Post on 16-Aug-2021
Both nivolumab (Opdivo®) and ipilimumab (Yervoy®) are approved as monotherapies for the treatment of unresectable or metastatic (advanced) melanoma (discussed in separate nursing tools). They are also approved for use together as combination therapy in this patient population. Nivolumab and ipilimumab each improve anticancer responses and patient survival by inhibiting molecules known as checkpoints to enhance the patient’s immune response to melanoma. Nivolumab inhibits the checkpoint known as programmed death receptor-1 (PD-1), and ipilimumab inhibits the checkpoint cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4).
Antitumor activity is improved with nivolumab/ipilimumab combination therapy compared with either monotherapy, but the risk and severity of immune-related adverse events (irAEs) is also heightened.
This document is part of an overall nursing toolkit intended to assist nurses in optimizing management of melanoma in patients receiving newer anti-melanoma therapies.
Nivolumab/Ipilimumab Combination Therapy for Melanoma: A Nursing Tool From the
Melanoma Nursing Initiative (MNI)
© 2017 The Melanoma Nursing Initiative. All rights reserved www.themelanomanurse.org
© 2017 The M
elanoma N
ursing Initiative. All rights reserved. C
ontent updated 3/22/2018.w
ww
.themelanom
anurse.org
Inspired By Patients . Empow
ered By Knowledge . Im
pacting Melanom
a
• Obtain pretreatm
ent laboratory tests (eg, adrenal function [ACTH
], clinical chemistries, liver function tests, and thyroid function tests) prior to
initiation of therapy and before each cycle
• Both nivolumab and ipilim
umab are m
onoclonal antibodies administered via intravenous infusion, using separate intravenous lines
• Both nivolumab and ipilim
umab are clear to opalescent, colorless to pale-yellow
solutions. Their vials should be discarded if the solutions are cloudy,discolored, or contains extraneous particulate m
atter (other than a few translucent-to-w
hite, proteinaceous particles)
• Neither ipilim
umab nor nivolum
ab should be coadministered w
ith each other or with other drugs through the sam
e intravenous line
• When adm
inistered in combination w
ith each other, nivolumab should be infused first, follow
ed on the same day by ipilim
umab, using separate
infusion bags and in-line filters with pore sizes of 0.2 – 1.2 m
icrons for each infusion
• Vials of nivolumab and ipilim
umab should not be shaken
• The dosing schema for the induction and m
aintenance phases is shown below
DRUG-DOSING/ADMINISTRATION
• Key to toxicity management:» Proactive assessment for early signs/symptoms of toxicity» Prompt intervention» irAEs are typically managed with selective use of steroids» In rare instances, toxicity may be steroid refractory, and additional immunosuppressive agents
may be necessary (mycophenolate mofetil, cyclophosphamide, etc)» Nivolumab/ipilimumab will likely be held or discontinued depending on severity and/or
persistence of the irAE» Referral to organ specialist should be considered
• irAEs associated with nivolumab/ipilimumab combination therapy can be categorized as most common,less common but serious, and others that are easily overlooked
• Table 1 lists these irAEs and the corresponding Care Step Pathways in Appendix 1. Other adverseevents associated with nivolumab/ipilimumab are shown in Appendix 2
© 2017 The Melanoma Nursing Initiative. All rights reserved www.themelanomanurse.org
Because nivolumab and ipilimumab are immunotherapies that work by enhancing the patient’s immune system, most adverse reactions associated with the combination are related to overactivity of the patient’s immune system (ie, immune-related adverse events [irAEs]). Various organ systems or tissues may be af-fected. Risk and severity of irAEs are relatively higher when nivolumab and ipilimumab are coadministered than when used as monotherapies. The irAEs associated with nivolumab/ipilimumab combination therapy also tend to have an earlier onset.
Inspired By Patients . Empowered By Knowledge . Impacting Melanoma
SIDE EFFECTS AND THEIR MANAGEMENT
irAE category Examples Location
Most common
Skin toxicities (pruritis, rash)Gastrointestinal toxicities
- Diarrhea/colitis - Mucositis/xerostomia
Hepatic toxicities - Elevated transaminases
Appendix 1
Less common but serious
Endocrinopathies - Hypophysitis (pituitary) - Thyroiditis - Diabetes
Pneumonitis
Appendix 1
Easily overlookedArthralgiaNeuropathyNephritis
Appendix 1
Table 1. List of Care Step Pathways for the management of immune-related AEs associated with nivolumab/ipilimumab therapy
• Nivolumab/ipilimumab-related irAEs may occur at any time, including after treatment completion ordiscontinuation. Continuing to monitor patients is critical
• Patients sometimes experience signs/symptoms that they think are due to “flu” or a cold, but thatactually represent an irAE or an infusion reaction
• Endocrinopathies often present with vague symptoms (fatigue, headache, and/or depression) thatcan easily be overlooked or initially misdiagnosed. Hypervigilance and follow-up is important on the part of both nurses and patients
• IrAEs may become apparent upon tapering of corticosteroids, since they can be suppressed ormasked by immunosuppressive therapy. Patients should be advised to be on the lookout for early signs of irAEs during the tapering period
• Unlike other irAEs, endocrinopathies usually do not resolve and may require lifelong hormonereplacement therapy
• Nurses should encourage patients to carry information about their nivolumab/ipilimumab regimenwith them at all times. This might be the nivolumab- and ipilimumab-specific wallet cards or at least emergency phone numbers and the side effects associated with the regimen. You may suggest they paperclip the wallet and insurance cards together so information about their regimen will be shared whenever they show the insurance card
• Advise patients to take pictures of any skin lesions for documentation
© 2017 The Melanoma Nursing Initiative. All rights reserved www.themelanomanurse.org
CLINICAL PEARLS
Inspired By Patients . Empowered By Knowledge . Impacting Melanoma
Q. After a well-tolerated induction with combination nivolumab/ipilimumab, a patient doeswell and has a significant response. The patient also does well on maintenance for ayear, with stable disease, but then the disease begins to progress. Can the patient bereinduced with nivolumab/ipilimumab?
A. Reinduction can be a reasonable consideration. Evaluation for a clinical trial should alwaysbe taken into consideration when contemplating a change in therapy. Reintroduction with asingle-agent immunotherapy is also an option.
Q. Should an asymptomatic endocrinopathy be treated?
A. A transient period of asymptomatic hyperthyroidism can sometimes be observed withPD-1 monotherapy, but it is more commonly observed early in treatment with combinationnivolumab/ipilimumab. In the Checkmate 067 phase 3 trial, 15% of patients treated with thecombination experienced hypothyroidism of any grade (Larkin J et al. N Engl J Med. 2015;373:23-34).
This period is typically followed by hypothyroidism which can be clinically detectable and oftenrequires permanent hormone replacement therapy.
Q. If it is not possible (because of side effects) for a highly motivated patient to completeall 4 induction cycles of combination nivolumab/ipilimumab, is it considered incompletetreatment or a “failure” to achieve a full course?
A. Goals of therapy are always geared toward safely adhering to the treatment plan regimen. Notall patients are able to complete all 4 induction infusions because of side effects. This is notdeemed as a failure, as every patient responds to immune stimulation differently and not allpatients can safely tolerate all 4 cycles.
Benefits have been observed with patients who did not complete all 4 induction cycles. In thephase 2 study, 68% of patients in a phase 2 trial who did not complete the induction regimenwith nivolumab/ipilimumab had objective responses (Postow MA et al. N Engl J Med. 2015;2006-2017). These data show that it is possible to have a therapeutic immune response withless than 4 cycles of induction.
© 2017 The Melanoma Nursing Initiative. All rights reserved www.themelanomanurse.org
QUESTIONS & ANSWERS
Q. If a patient does not finish all 4 doses of induction, can they go on to receivemaintenance nivolumab?
A. This decision is made on an individual basis. Some safety factors taken into considerationare: (1) the severity of immune related side effects; (2) the time it took for the side effectsto resolve; and (3) the specific side effects that contributed to the truncation of induction.Oftentimes, patients have been able to successfully transition to maintenance nivolumab.
© 2017 The Melanoma Nursing Initiative. All rights reserved www.themelanomanurse.org
QUESTIONS & ANSWERS(CONTINUED)
© 2017 The Melanoma Nursing Initiative. All rights reserved www.themelanomanurse.org
Financial AssistanceBMS Access Support 1 (800) 861-0048 http://www.bmsaccesssupport.bmscustomerconnect.com/patient
Additional Patient ResourcesFor more information about this therapy and support:Guide to Opdivo/Yervoy Combination Treatment https://www.opdivo.com/servlet/servlet.FileDownload?file=00Pi000000o0a9ZEAQ
Additional Information ResourcesAIM at Melanoma Foundation (Nurse on Call, patient symposia, drug resources, etc) http://www.AIMatMelanoma.org
American Cancer Society Resource Section https://www.cancer.org/treatment/treatments-and-side-effects/treatment-types/immunotherapy/immune-checkpoint-inhibitors.html
PATIENT RESOURCES
© 2017 The Melanoma Nursing Initiative. All rights reserved. Content updated 3/22/2018. www.themelanomanurse.org
• Food and Drug Administration & Bristol-Myers Squibb. Risk Evaluation and MitigationStrategy (REMS) for ipilimumab (Yervoy); February 2012. Includes wallet card etc. Available at: https://www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM249435.pdf
• Boutros C, Tarhini A, Routier E, et al. Safety profiles of anti-CTLA-4 and anti-PD-1antibodies alone and in combination. Nat Rev Clin Oncol. 2016;13:473-486.
• Friedman CF, Proverbs-Singh TA, Postow MA. Treatment of the immune-relatedadverse effects of immune checkpoint inhibitors: a review. JAMA Oncol. 2016;2:1346-1353.
• Rubin KM. Managing immune-related adverse events to ipilimumab: a nurse’s guide.Clin J Oncol Nurs. 2012;16:E69-E75.
• Villadolid J, Amin A. Immune checkpoint inhibitors in clinical practice: update onmanagement of immune-related toxicities. Transl Lung Cancer Res. 2015;4:560-577.
• Madden KM, Hoffner B. Ipilimumab-based therapy: consensus statement fromthe faculty of the Melanoma Nursing Initiative on managing adverse events with ipilimumab monotherapy and combination therapy with nivolumab. Clin J Oncol Nurs. 2017;21(suppl):30-41.
• Opdivo® [package insert]. Princeton, NJ: Bristol-Myers Squibb Company; 2018.Available at: http://packageinserts.bms.com/pi/pi_opdivo.pdf
• Yervoy® [package insert]. Princeton, NJ: Bristol-Myers Squibb Company; 2017.Available at: http://packageinserts.bms.com/pi/pi_yervoy.pdf
ADDITIONAL RESOURCES
Click here for downloadable action plans to customize for your patients
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elanoma N
ursing Initiative. All rights reserved
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elanomanurse.org
APPENDIX 1
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elanoma N
ursing Initiative. All rights reserved
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elanomanurse.org
Care Step Pathw
ay-Skin Toxicities
Nursing Assessm
ent
Look:-
Does the patient appear uncom
fortable?-
Does the patient appear unw
ell?-
Is there an obvious rash?-
Is the patient scratching during the visit?-
Is skin integrity intact?-
Are there skin changes?o
Xerosiso
Changes in skin pigm
ent or color-
Is there oralinvolvement of the rash?
Grading Toxicity
MAC
ULO
PAPU
LAR
RA
SH (aka m
orbilliformrash)
Definition: A
disorder characterized by the presence of macules (flat) and papules (elevated); frequently affecting the upper trunk, spreading centripetally
and associated w
ith pruritus
PRU
RITU
SD
efinition: A disorder characterized by an intense itching sensation
Listen:-
Does the patient have pruritus
with or w
ithout rash?Is there a rash w
ith or without pruritus ?
-A
re symptom
s interfering with A
DLs?
-W
ith sleep?-
Have sym
ptoms w
orsened?
Recognize:
-Is there a history of derm
atitis, pre-existing skinissues (psoriasis, w
ounds, etc.)?-
Laboratory abnormalities consistent w
ith otheretiologies (e.g., eosinophils on com
plete bloodcount, liver function abnorm
alities)
Managem
ent
Overall Strategy
-Assess for other etiology of rash: ask patient about new
medications,herbals, supplem
ents, alternative/complem
entarytherapies, lotions, etc.
Grade 1 (M
ild)-
Imm
unotherapyto continue
-O
ral antihistamines w
ill be used in som
e patients-
Topicalcorticosteroids will be used in
some patients (0.5 m
g/kg)-
Advise vigilant skin care o
Increase to twice daily
applications of non-steroidalm
oisturizersor em
ollientsapplied to m
oist skino
Moisturizers w
ith ceramides and
lipids are advised;however, if
cost is an issue, petroleumjelly
is also effectiveo
Soothing m
ethods
Cool cloth applications
Topicals w
ith cooling agentssuch as m
enthol orcamphor
R
efrigerating products priorto application
oA
void hot water;bathe orshow
erw
ith tepid water
oK
eep fingernails shorto
Cool tem
peraturefor sleep
-A
dvise strict sun protection -
Monitor vigilantly. Instruct patient &
family to call clinic w
ith any sign ofw
orsening rash/symptom
s. Anticipate
office visit for evaluation-
Assess patient&
family
understanding of skin care recom
mendations and rationale
oIdentify barriers to adherence
Grade 2 (M
oderate)-
Ipilimum
ab will be w
ithheld forany Grade
2 event-
Oral corticosteroids (0.5
mg/kg–1.0m
g/kg)and oralantihistam
ines/oral anti-pruriticsto be used
-C
onsider dermatology consult
-P
atient education:o
Proper adm
inistration of oralcorticosteroids
Take with food
Take early in day
C
oncomitant m
edications may
be prescribed
H2 blocker
A
ntibiotic prophylaxis-
Advise vigilant skin careo
Gentle skin care
oTepid baths;oatm
eal baths-
Advise strict sun protection
-A
ssesspatient &
family understanding of
toxicity and rationale for treatmenthold
oIdentify barriers to adherence
Grades 3-4 (Severe or Life-Threatening)
-N
ivolumab
to be withheld forG
rade 3 rash orconfirm
edS
JN or TE
N-
Ipilimum
ab to be discontinued for any Grade
3/4 event, and nivolumab forG
rade 4 rash orconfirm
ed SJS
or TEN
-P
embrolizum
ab or nivolumab to be
discontinued for any Grade 3/4 event that
recurs, persists≥12 w
eeks, orfor inability to reduce steroid dose to ≤10 m
g prednisone orequivalent w
ithin 12 weeks
-A
nticipate hospitalization and initiation of IVcorticosteroids (1.5–2.0
mg/kg)
-A
nticipate dermatology consult +/-biopsy
-P
rovide anticipatory guidance: o
Rationale for hospitalization and
treatment discontinuation
oR
ationale for prolonged steroid tapero
Side
effects ofhigh-dose steroidso
Risk
of opportunistic infectionand
need for antibiotic prophylaxis
oE
ffectson
blood sugars, muscle
atrophy, etc.-
Assess
patient &fam
ily understanding oftoxicity and rationale for treatm
entdiscontinuation o
Identify barriers to adherence,specifically com
pliance with steroids
when transitioned to oral corticosteroids
Grade 1 (M
ild)M
acules/papules covering <10%
BS
Aw
ith or without sym
ptoms
(e.g., pruritus, burning, tightness)
Grade 2 (M
oderate)M
acules/papules covering 10-30%B
SA
with or w
ithout symptom
s (e.g.,pruritus, burning, tightness); lim
iting instrum
ental AD
Ls
Grade 3 (Severe)
Macules/papules covering >30%
B
SA
with or w
ithout associated sym
ptoms; lim
iting self-care ADLs;
skin sloughing covering <10%
BS
A
Grade 4 (Potentially Life-Threatening)
Papules/pustules covering any %
BS
A w
ith or w
ithout symptom
s and associated with
superinfection requiring IV antibiotics; skin
sloughing covering 10-30% BS
A
Grade 5 (D
eath)
Grade 1 (M
ild)M
ild or localized; topical intervention indicated
Grade 2 (M
oderate)Intense or w
idespread; interm
ittent; skin changes from
scratching (e.g., edema,
papulation, excoriations, lichenification, oozing/crusts); lim
iting instrumental A
DLs
Grade 3 (Severe)
Intense or widespread; constant;
limiting self-care A
DL or sleep
Grade 4 (Potentially Life-Threatening)
Grade 5 (D
eath)
Intervention in at-risk patients-
Advise gentle skin care:o
Avoid soap. Instead,use non-soap
cleansersthat are fragrance-and
dye-free (use mild soap on the
axillae, genitalia, and feet)o
Daily applications
of non-steroidalm
oisturizersor em
ollientscontaining hum
ectants (urea,glycerin)
oA
pplym
oisturizers and emollients
in the direction of hair growth to
minim
ize development of folliculitis
-A
dvise sun-protective measures
-A
ssess patient& fam
ilyunderstanding
ofprevention strategies and rationaleo
Identify barriers to adherence
RED FLAGS:
-Extensive
rash (>50% BSA), or rapidly progressive
-O
ral involvement
-Concern for suprainfection
AD
Ls = activities ofdaily living;BS
A=
bodysurface area;S
JN=
Stevens-Johnson syndrom
e; TEN
=toxic
epidermal necrolysis
Copyright ©
2017 Melanom
a Nursing Initiative.
Skin Toxicities Page 1 of 2
© 2017 The M
elanoma N
ursing Initiative. All rights reserved
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w.them
elanomanurse.org
Care Step Pathw
ay-Skin Toxicities
Nursing Assessm
ent
Look:-
Does the patient appear uncom
fortable?-
Does the patient appear unw
ell?-
Is there an obvious rash?-
Is the patient scratching during the visit?-
Is skin integrity intact?-
Are there skin changes?o
Xerosiso
Changes in skin pigm
ent orcolor-
Is there oralinvolvement of the rash?
Grading Toxicity
MAC
ULO
PAPU
LAR
RA
SH (aka
morbilliform
rash)D
efinition: Adisorder characterized by
the presence ofmacules (flat) and papules (elevated); frequently
affecting the upper trunk, spreading centripetallyand associated
with pruritus
PRU
RITU
SD
efinition: Adisorder characterized by an intense itching sensation
Listen:-
Does the patient have pruritus
with or w
ithout rash? Is there a rash w
ith or withoutpruritus?
-A
re symptom
s interfering with A
DLs?
-W
ith sleep? -
Have sym
ptoms w
orsened?
Recognize:
-Is there a history ofderm
atitis, pre-existing skin issues (psoriasis, w
ounds, etc.)?-
Laboratory abnormalities consistent w
ith otheretiologies (e.g.,eosinophils
on complete blood
count, liver function abnormalities)
Managem
ent
Overall Strategy
-Assess for other etiology of rash: ask patient about new
medications, herbals, supplem
ents, alternative/complem
entary therapies, lotions, etc.
Grade 1 (M
ild)-
Imm
unotherapy to continue-
Oral antihistam
ines will be used in
some patients
-Topical corticosteroids w
ill be used in som
e patients -
Advise vigilant skin careo
Increase to twice daily
applications of non-steroidal m
oisturizers or emollients
applied to moist skin
oM
oisturizers with ceram
ides and lipids are advised; how
ever, if cost is an issue, petroleum
jelly is also effective
oS
oothing methods
C
ool cloth applications
Topicals with cooling agents
such as menthol or cam
phor
Refrigerating products prior
to applicationo
Avoid hot w
ater; bathe or shower
with tepid w
atero
Keep fingernails short
oC
ool temperature for sleep
-A
dvise strict sun protection-
Monitor vigilantly. Instruct patient &
family to call clinic w
ith any sign of w
orsening rash/symptom
s. Anticipate
office visit for evaluation-
Assess patient &
family
understanding of skin care recom
mendations and rationale
oIdentify barriers to adherence
Grade 2 (M
oderate)-
Ipilimum
ab will be w
ithheld for any Grade 2
event-
Oral corticosteroids (0.5 m
g/kg–1.0 mg/kg)
and oral antihistamines/oral anti-pruritics to
be used-
Consider derm
atology consult-
Patient education:o
Proper adm
inistration of oral corticosteroids
Take with food
Take early in day
C
oncomitant m
edications may be
prescribed
H2 blocker
A
ntibiotic prophylaxis-
Advise vigilant skin careo
Gentle skin care
oTepid baths; oatm
eal baths-
Advise strict sun protection
-A
ssess patient & fam
ily understanding of toxicity and rationale for treatm
ent holdo
Identify barriers to adherence
Grades 3-4 (Severe or Life-Threatening)
-N
ivolumab
to be withheld for G
rade 3 rash orconfirm
edS
JN or TE
N-
Ipilimum
ab to be discontinued for any Grade
3/4 event, and nivolumab for G
rade 4 rash orconfirm
ed SJS
or TEN
-P
embrolizum
ab or nivolumab t o be
di scontinued for any Grade 3/4 event that
recurs, persists ≥12 weeks, orfor inability to
r educe steroid dose to ≤10 mg prednisone or
equivalent within 12 w
eeks-
Anticipate hospitalization and initiation of IV
corticosteroids (1.5–2.0m
g/kg)-
Anticipate derm
atology consult +/-biopsy-
Provide anticipatory guidance:o
Rationale for hospitalization and
treatment discontinuation
oR
ationale for prolonged steroid tapero
Side
effects of high-dose steroidso
Risk of opportunistic infection and
needf or antibiotic prophylaxis
oE
ffects on blood sugars, muscle
at rophy, etc.-
Assess patient &
family understanding of
toxicity and rationale for treatment
discontinuationo
Identify barriers to adherence,specifically com
pliance with steroids
when transitioned to oral corticosteroids
Grade 1 (M
ild)M
acules/papules covering <10%
BS
Aw
ith or without sym
ptoms
(e.g., pruritus, burning,tightness)
Grade 2 (M
oderate)M
acules/papules covering 10-30%B
SA
with or w
ithout symptom
s (e.g.,pruritus, burning,tightness); lim
iting instrum
entalAD
Ls
Grade 3 (Severe)
Macules/papules covering >30%
B
SA
with or w
ithout associated sym
ptoms;lim
iting self-care ADLs;
skin sloughing covering <10%
BS
A
Grade 4 (Potentially Life-Threatening)
Papules/pustules covering any %
BS
A w
ith or w
ithout symptom
sand associated w
ith superinfection requiring IV
antibiotics; skin sloughing covering 10-30%
BSA
Grade 5 (D
eath)
Grade 1 (M
ild)M
ild or localized; topicalintervention indicated
Grade 2 (M
oderate)Intense or w
idespread;interm
ittent; skin changesfrom
scratching (e.g., edema,
papulation, excoriations,lichenification, oozing/crusts);lim
iting instrumental A
DLs
Grade 3 (Severe)
Intense or widespread;constant;
limiting self-care A
DL orsleep
Grade 4 (Potentially Life-Threatening)
Grade 5 (D
eath)
Intervention in at-risk patients-
Advise gentle skin care:o
Avoid soap. Instead, use non-soap
cleansers that are fragrance-anddye-free (use m
ild soap on theaxillae, genitalia, and feet)
oD
aily applications of non-steroidalm
oisturizers or emollients
containing humectants (urea,
glycerin)o
Apply m
oisturizers and emollients
in the direction of hair growth to
minim
ize development of folliculitis
-A
dvise sun-protective measures
-A
ssess patient & fam
ily understandingof prevention strategies and rationaleo
Identify barriers to adherence
RED FLAGS:
-Extensive rash (>50%
BSA), or rapidly progressive-
Oral involvem
ent-
Concern for suprainfection
AD
Ls = activities of daily living; BS
A=
body surface area;SJN
=S
tevens-Johnson syndrome; TE
N = toxic epiderm
al necrolysis
Copyright ©
2017 Melanom
a Nursing Initiative.
Skin Toxicities Page 2 of 2
Care Step Pathw
ay -Gastrointestinal Toxicity: D
iarrhea and Colitis
Nursing Assessm
entLook:-
Does the patient appear w
eak?-
Has the patient lost w
eight?-
Does the patient appear dehydrated?
-D
oes the patient appear in distress?
Grading Toxicity
Diarrhea (increased frequency, loose, large volum
e, or liquidy stools)
Colitis (inflam
mation of the intestinal lining)
Listen:-
Quantity &
quality of bowel m
ovements (e.g., change in/
increased frequency over baseline): solid, soft, or liquid diarrhea; dark or bloody stools; or stools that float
-Fever
-A
bdominal pain or cram
ping-
Increased fatigue-
Upset stom
ach, nausea, or vomiting
-B
loating/increased gas-
Decreased appetite or food aversions
Recognize:
-S
erum chem
istry/hematology abnorm
alities-
Infectious vs imm
une-related adverse eventcausation
-P
eritoneal signs of bowel perforation (i.e.,
pain, tenderness, bloating)
Managem
ent(including Anticipatory G
uidance)
Overall Strategy:
-R
ule out infectious, non-infectious, disease-related etiologies
Grade 1 (M
ild)-
May continue im
munotherapy
Diet m
odifications (very important):
-Institute bland diet;decrease fiber, uncooked fruits/vegetables, red m
eats, fats, dairy, oil, caffeine,alcohol, sugar
Grade 2 (M
oderate)-
Send stool sam
ple forC difficile
testing, culture, andova and
parasite -
Imm
unotherapyto be w
ithhelduntil G
rade ≤1 orpatient’sbaseline (ipilim
umab, pem
brolizumab, nivolum
ab)-
Provide anti-diarrheals: Im
odium®
(loperamide)orLom
otil ®
(diphenoxylate/atropine)-
Ifupper orlower G
Isymptom
spersist >5–7 days
oO
ral steroids* to be started (prednisone 0.5m
g–1m
g/kg/day or equivalent)o
After control of sym
ptoms, a ≥4-w
eek steroid* taper will
be initiated-
Imm
unotherapyto
be discontinued ifGrade 2
symptom
spersist≥6 w
eeks (ipilimum
ab)or≥12 w
eeks (pembrolizum
ab,nivolum
ab),or for inability to reduce steroid dose to ≤7.5 mg
(ipilimum
ab) or≤10 m
g prednisone or equivalent(pem
brolizumab, nivolum
ab) within 12 w
eeks
Diet m
odification:-
Institute bland dietlow in fiber, residue,and fat (B
RA
T[B
ananas, Rice, A
pplesauce,Toast] diet)-
Decrease fiber, uncooked fruitand vegetables, red m
eats,fats,dairy, oil,caffeine, alcohol, sugar
-A
void laxativesor stool softeners
-A
dvance diet slowly
assteroids
are tapered,* reduced to lowdoses
and assessfor loose or liquid stoolfor severaldays or
longer-
Steroids* to be tapered slow
ly over at least 4 weeks
(Moderate) persistent orrelapsed
symptom
s with steroid*
taper-
Consider gastroenterology consultfor possible intervention
(flex sig/colonoscopy/endoscopy)-
IV steroids*
to be started at1m
g/kg/day-
Imm
unotherapyto
be helduntil≤G
rade 1-
Controlsym
ptoms, then ≥4-w
eeksteroid* taper
-R
ecurrent diarrhea is more likely w
hen treatmentis
restarted
Grades 3-4
(Severe or Life-Threatening)-
Onset: o
Continued dietm
odification, anti-diarrheals,and steroidtitration
-Im
munotherapy:
oG
rade 3: Pembrolizum
abor nivolum
abto be w
ithheld w
hen used as singleagent;ipilim
umab
to be discontinued
as single agent andnivolum
ab when given
with ipilim
umab
oG
rade 4: Ipilimum
ab and/or PD-1 inhibitorto be
discontinued-
Does
of steroids*to
be increased:o
Steroids* 1-2 m
g/kg/day prednisone orequivalent:m
ethylprednisolone (Solu-M
edrol ®)1 g IV(daily
divided)doses
-H
ospitalization-
GI consultation
-A
ssess forperitoneal signs, perforation (NP
O &
abdominalx-
ray, surgical consultprn)-
Use caution w
ith analgesics (opioids) and anti-diarrhealm
edications
Steroid* refractory:(if not responsive w
ithin 72 hours to high-dose IV
steroid* infusion)-
Infliximab
(Rem
icade®)5
mg/kg infusion
may
be considered-
May
require ≥1 infusion to manage sym
ptoms
(may
re-adm
inister at week 2 &
week
6)-
Avoid w
ith bowelperforation or sepsis
-P
PD
(tuberculin)testing not required in this setting -
Infliximab infusion delay m
ay have life-threatening consequences
Diet m
odification:-
Very strict w
ith acute symptom
s:clear liquids;verybland, low
fiberand low residue (B
RA
T diet)-
Advance dietslow
ly as steroids* reduced to low doses
-S
teroids*to be tapered slow
ly over at least 4 weeks
-Supportive
medications
for symptom
atic managem
ent:o
Loperamide:2
capsulesatthe onset &
1 with each
diarrhea stoolthereafter, with a m
aximum
of 6 perdayo
Diphenoxylate/atropine 1-4
tabletsper day
oS
imethicone
when necessary
Grade 1 (M
ild)A
symptom
atic; clinical or diagnosticobservation only; intervention not indicated
Grade 2 (M
oderate)A
bdominal pain;blood or m
ucus in stoolG
rade 3 (Severe)Severe abdom
inal pain; change in bow
el habits; medical intervention
indicated; peritonealsigns
Grade 4 (Potentially Life-Threatening)
Life-threatening(e.g., hem
odynamic
collapse); urgent intervention indicated
Grade 5 (D
eath)
Nursing Im
plementation:
-C
ompare baseline assessm
ent:grade & docum
ent bowel frequency
-E
arly identification and evaluation of patient symptom
s-
Grade sym
ptom &
determine level ofcare and interventions required
-E
arly intervention with lab w
ork and office visit ifcolitissym
ptoms are
suspected
*Steroid
taperinstructions/calendarasa
guidebutnotan
absolute-
Tapershouldconsiderpatient’s
currentsymptom
profile-
Close
follow-up
inperson
orbyphone,based
onindividualneed
&sym
ptomatology
-A
nti-acidtherapy
dailyas
gastriculcerprevention
while
onsteroids
-R
eviewsteroid
medication
sideeffects:m
oodchanges
(anger,reactive,hyperaware,euphoric,m
ania),increasedappetite,interrupted
sleep,oralthrush,fluidretention
-B
ealertto
recurringsym
ptoms
assteroids
taperdown
& reportthem
(tapermay
needto
beadjusted)
Long-termhigh-dose
steroids:-
Considerantim
icrobialprophylaxis(sulfam
ethoxazole/trimethoprim
double dose M/W
/F; single dose ifuseddaily) or alternative ifsulfa-allergic (e.g.,atovaquone [M
epron®]1500 m
g podaily)
-C
onsideradditionalantiviraland antifungalcoverage-
Avoid
alcohol/acetaminophen
orotherhepatoxins
Grade 1 (M
ild)-
Increase of <4 stools/day overbaseline
-M
ild increase in ostomy output
compared w
ithbaseline
Grade 2 (M
oderate)-
Increase of 4–6 stools/day overbaseline
-M
oderate increase of output inostom
y compared w
ithbaseline
Grade 3 (Severe)
-Increase of ≥7 stools/day
overbaseline; incontinence
-H
ospitalization indicated-
Severe increase in ostom
y outputcom
pared with
baseline-
Limiting self-care A
DLs
Grade 4 (Potentially Life-Threatening)
-Life-threatening
(e.g., perforation, bleeding,ischem
ic necrosis, toxic megacolon)
-U
rgent intervention required
Grade 5 (D
eath)
RED FLAGS:
-Change
in gastrointestinalfunction, decreased appetite-
Bloating, nausea-
More frequent stools, consistency
change fromloose to liquid
-Abdom
inal pain-
Fever
AD
Ls = activities ofdaily living;PD
-1=
programm
ed cell death protein 1
Copyright ©
2017 Melanom
a Nursing Initiative.
© 2017 The M
elanoma N
ursing Initiative. All rights reserved
ww
w.them
elanomanurse.org
Gastrointestinal Toxicity Page 1 of 3
Care Step Pathw
ay-G
astrointestinal Toxicity:Diarrhea
and Colitis
Nursing Assessm
entLook:-
Does the patient appear w
eak?-
Has the patient lost w
eight?-
Does the patient appear dehydrated?
-D
oes the patient appear in distress?
Grading Toxicity
Diarrhea (increased frequency, loose, large volum
e, or liquidystools)
Colitis (inflam
mation of the intestinallining)
Listen:-
Quantity &
quality of bowelm
ovements
(e.g., change in/increased frequency over baseline): solid, soft,or liquid diarrhea;dark orbloody stools;or stools that float
-Fever
-A
bdominal pain or cram
ping-
Increased fatigue-
Upset stom
ach,nausea,or vomiting
-A
bdominal pain or cram
ping-
Bloating/increased gas
-D
ecreased appetite orfood aversions
Recognize:
-S
erum chem
istry/hematology abnorm
alities-
Infectious vsim
mune-related adverse event
causation-
Peritonealsigns
of bowel perforation (i.e.,
pain, tenderness, bloating)
Managem
ent(including Anticipatory G
uidance)
Overall Strategy:
-R
ule out infectious, non-infectious, disease-related etiologies
Grade 1 (M
ild)-
May continue im
munotherapy
Diet m
odifications (very important):
-Institute bland diet;decrease fiber, uncookedfruits/vegetables, red m
eats, fats, dairy, oil ,caffeine, alcohol, sugar
Grade 2 (M
oderate)-
Send stool sam
ple for C difficile
testing, culture, andova and
parasit e-
Imm
unotherapy to be withheld until G
rade ≤1 or patient’sbaseline (ipilim
umab, pem
brolizumab, nivolum
ab)-
Provide anti-diarrheals: Im
odium®
(loperamide) orLom
otil ®
(diphenoxylate/atropine)-
Ifupper or lower G
I symptom
s persist >5–7 dayso
Oral steroids* to be started (prednisone 0.5
mg–1
mg/kg/day or equivalent)
oA
fter control of symptom
s, a ≥4-week steroid* taper w
illbe initiated
-Im
munotherapy to be discontinued ifG
rade 2sym
ptoms
persist≥6 weeks (ipilim
umab) or ≥12 w
eeks (pembrolizum
ab,nivolum
ab), or for inability to reduce steroid dose to ≤7.5 mg
(ipilimum
ab) or ≤10 mg prednisone or equivalent
(pembrolizum
ab, nivolumab) w
ithin 12 weeks
Diet m
odification:-
Institute bland diet low in fiber, residue, and fat (B
RA
T[B
ananas, Rice, A
pplesauce, Toast] diet)-
Decrease fiber, uncooked fruitand vegetables, red m
eats,fats, dairy, oil, caffeine, alcohol, sugar
-A
void laxatives or stool softeners-
Advance diet slow
ly as steroidsare tapered,* reduced to low
dosesand assess for loose or liquid stool for several days or
longer-
Steroids* to be tapered slow
ly over at least 4 weeks
(Moderate) persistent or relapsed sym
ptoms w
ith steroid* taper-
Consider gastroenterology consult for possible intervention
( flex sig/colonoscopy/endoscopy)-
IV steroids*
to be started at1m
g/kg/day-
Imm
unotherapyto be held
until ≤Grade 1
-C
ontrol symptom
s, then ≥4-week
steroid* taper-
Recurrent diarrhea is m
ore likely when treatm
ent isrestarted
Grades 3-4
(Severe or Life-Threatening)-
Onset:o
Continued diet m
odification, anti-diarrheals, and steroid titration
-Im
munotherapy:
oG
rade 3: Pem
brolizumab or nivolum
ab to be withheld
when used as single agent; ipilim
umab to be
discontinued as single agent and nivolumab w
hen given w
ith ipilimum
abo
Grade 4: Ipilim
umab and/or P
D-1 inhibitor to be
discontinued-
Dosage of steroids* to be increased:o
Steroids* 1-2 m
g/kg/day prednisone or equivalent: m
ethylprednisolone (Solu-M
edrol ®)1 g IV (daily divided)
doses-
Hospitalization
-G
I consultation-
Assess for peritoneal signs, perforation (N
PO
& abdom
inal x- ray, surgical consult prn)
-U
se caution with analgesics (opioids) and anti-diarrheal
medications
Steroid* refractory:(if not responsive w
ithin 72 hours to high-dose IV
steroid* infusion)-
Infliximab
(Rem
icade®)5
mg/kg infusion
may be considered
-M
ay require ≥1 infusion to manage sym
ptoms (m
ay re-adm
inister at week 2 &
week 6)
-A
void with bow
el perforation or sepsis-
PP
D(tuberculin) testing not required in this setti ng
-I nflixim
ab infusion delay may have life-threatening
c onsequences
Diet m
odification:-
Very strict w
ith acute symptom
s:clear liquids;very bland, lowfiber and low
residue (BR
AT diet)
-A
dvance diet slowly as steroids* reduced to low
doses-
Steroids* to be tapered slow
ly over at least 4 weeks
-Supportive m
edicationsfor sym
ptomatic m
anagement:
oLoperam
ide:2capsules
at the onset & 1 w
ith eac hdiarrhea stool thereafter, w
ith a maxim
um of 6 per day
oD
iphenoxylate/atropine 1-4tablets
per dayo
Sim
ethiconew
hen necessary
Grade 1 (M
ild)A
symptom
atic; clinical ordiagnosticobservation only;intervention notindicated
Grade 2 (M
oderate)A
bdominal pain;blood orm
ucus in stoolG
rade 3 (Severe)Severe abdom
inal pain; change inbow
el habits; medical intervention
indicated; peritonealsigns
Grade 4 (Potentially Life-Threatening)
Life-threatening(e.g., hem
odynamic
collapse); urgent intervention indicated
Grade 5 (D
eath)
Nursing Im
plementation:
-C
ompare baseline assessm
ent:grade & docum
ent bowel frequency
-E
arly identification and evaluation of patient symptom
s-
Grade sym
ptom &
determine level ofcare and interventions required
-E
arly intervention with lab w
ork and office visit ifcolitissym
ptoms are
suspected
*Steroid
taperinstructions/calendarasa
guidebutnotan
absolute-
Tapershouldconsiderpatient’s
currentsymptom
profile-
Close
follow-up
inperson
orbyphone,based
onindividualneed
&sym
ptomatology
-A
nti-acidtherapy
dailyas
gastriculcerprevention
while
onsteroids
-R
eviewsteroid
medication
sideeffects:m
oodchanges
(anger,reactive,hyperaware,euphoric,m
ania),increasedappetite,interrupted
sleep,oralthrush,fluidretention
-B
ealertto
recurringsym
ptoms
assteroids
taperdown
& reportthem
(tapermay
needto
beadjusted)
Long-termhigh-dose
steroids:-
Considerantim
icrobialprophylaxis(sulfam
ethoxazole/trimethoprim
double dose M/W
/F; single dose ifuseddaily) or alternative ifsulfa-allergic (e.g.,atovaquone [M
epron®]1500 m
g podaily)
-C
onsideradditionalantiviraland antifungalcoverage-
Avoid
alcohol/acetaminophen
orotherhepatoxins
Grade 1 (M
ild)-
Increase of <4 stools/day overbaseline
-M
ild increase in ostomy output
compared
with
baseline
Grade 2 (M
oderate)-
Increase of4–6 stools/day overbaseline
-M
oderate increase of outputinostom
y compared w
ithbaseline
Grade 3 (Severe)
-Increase of≥7 stools/day
overbaseline; incontinence
-H
ospitalization indicated-
Severe increase in ostom
youtput
compared
with
baseline-
Limiting self-care A
DLs
Grade 4 (Potentially Life-Threatening)
-Life-threatening
(e.g., perforation, bleeding,ischem
icnecrosis, toxic
megacolon)
-U
rgent intervention required
Grade 5 (D
eath)
RED FLAGS:
-Change
in gastrointestinalfunction, decreased appetite-
Bloating, nausea-
More frequent stools, consistency
change fromloose to liquid
-Abdom
inal pain-
Fever
AD
Ls = activities ofdaily living;PD
-1=
programm
ed cell death protein 1
Copyright ©
2017 Melanom
a Nursing Initiative.
© 2017 The M
elanoma N
ursing Initiative. All rights reserved
ww
w.them
elanomanurse.org
Gastrointestinal Toxicity Page 2 of 3
C
are Step Pathway -G
astrointestinal Toxicity: Diarrhea and C
olitis
Nursing Assessm
entLook:-
Does the patient appear w
eak?-
Has the patient lost w
eight?-
Does the patient appear dehydrated?
-D
oes the patient appear in distress?
Grading Toxicity
Diarrhea (increased frequency, loose, large volum
e, or liquidy stools)
Colitis (inflam
mation of the intestinal lining)
Listen:-
Quantity &
quality of bowel m
ovements (e.g., change
in/increased frequency over baseline): solid, soft,or liquid diarrhea;dark or bloody stools;or stools that float
-Fever
-A
bdominal pain or cram
ping-
Increased fatigue-
Upset stom
ach,nausea,or vomiting
-A
bdominal pain or cram
ping-
Bloating/increased gas
-D
ecreased appetite or food aversions
Recognize:
-S
erum chem
istry/hematology abnorm
alities-
Infectious vs imm
une-related adverse eventcausation
-P
eritoneal signs of bowel perforation (i.e.,
pain, tenderness, bloating)
Managem
ent(including Anticipatory G
uidance)
Overall Strategy:
-R
ule out infectious, non-infectious, disease-related etiologies
Grade 1 (M
ild)-
May continue im
munotherapy
Diet m
odifications (very important):
-Institute bland diet;decrease fiber, uncooked fruits/vegetables, red m
eats, fats, dairy, oil, caffeine, alcohol, sugar
Grade 2 (M
oderate)-
Send stool sam
ple for C difficile
testing, culture, andova and
parasite -
Imm
unotherapy to be withheld until G
rade ≤1 or patient’s baseline (ipilim
umab, pem
brolizumab, nivolum
ab) -
Provide anti-diarrheals: Im
odium®
(loperamide) orLom
otil ®
(diphenoxylate/atropine)-
Ifupper or lower G
I symptom
s persist >5–7 days o
Oral steroids* to be started (prednisone 0.5
mg–1
mg/kg/day or equivalent)
oA
fter control of symptom
s, a ≥4-week steroid* taper w
ill be initiated
-Im
munotherapy to be discontinued ifG
rade 2sym
ptoms
persist≥6 weeks (ipilim
umab) or ≥12 w
eeks (pembrolizum
ab, nivolum
ab), or for inability to reduce steroid dose to ≤7.5 mg
(ipilimum
ab) or ≤10 mg prednisone or equivalent
(pembrolizum
ab, nivolumab) w
ithin 12 weeks
Diet m
odification:-
Institute bland diet low in fiber, residue, and fat (B
RA
T [B
ananas, Rice, A
pplesauce, Toast] diet)-
Decrease fiber, uncooked fruitand vegetables, red m
eats, fats, dairy, oil, caffeine, alcohol, sugar
-A
void laxatives or stool softeners-
Advance diet slow
ly as steroidsare tapered,* reduced to low
doses
and assess for loose or liquid stool for several days or longer
-S
teroids* to be tapered slowly over at least 4 w
eeks
(Moderate) persistent or relapsed sym
ptoms w
ith steroid* taper-
Consider gastroenterology consult for possible intervention
(flex sig/colonoscopy/endoscopy)-
IV steroids*
to be started at1m
g/kg/day-
Imm
unotherapyto be held
until ≤Grade 1
-C
ontrol symptom
s, then ≥4-week
steroid* taper-
Recurrent diarrhea is m
ore likely when treatm
ent is restarted
Grades 3-4
(Severe or Life-Threatening)-
Onset: o
Continued diet m
odification, anti-diarrheals,and steroidtitration
-Im
munotherapy:
oG
rade 3: Pembrolizum
abor nivolum
abto be w
ithheld w
hen used as singleagent; ipilim
umab
to be discontinued
as single agent andnivolum
ab when given
with ipilim
umab
oG
rade 4: Ipilimum
ab and/or PD-1 inhibitorto be
discontinued-
Does
of steroids*to be increased:
oS
teroids* 1-2 mg/kg/day prednisone or equivalent:
methylprednisolone (S
olu-Medrol ®)1 g IV
(dailydivided)
doses-
Hospitalization
-G
I consultation-
Assess for peritoneal signs, perforation (N
PO
& abdom
inalx-ray, surgical consult prn)
-U
se caution with analgesics (opioids) and anti-diarrheal
medications
Steroid* refractory:(if not responsive w
ithin 72 hours to high-dose IV
steroid* infusion)-
Infliximab
(Rem
icade®)5
mg/kg infusion
may be considered
-M
ay require ≥1 infusion to manage sym
ptoms (m
ay re-adm
inister at week 2 &
week 6)
-A
void with bow
el perforation or sepsis-
PP
D(tuberculin) testing not required in this setting
-Inflixim
ab infusion delay may have life-threatening
consequences
Diet m
odification:-
Very strict w
ith acute symptom
s:clear liquids;very bland, low
fiber and low residue (B
RA
T diet)-
Advance diet slow
ly as steroids* reduced to low doses
-S
teroids* to be tapered slowly over at least 4 w
eeks -
Supportive medications
for symptom
atic managem
ent:o
Loperamide:2
capsulesat the onset &
1 with each
diarrhea stool thereafter, with a m
aximum
of 6 per dayo
Diphenoxylate/atropine 1-4
tabletsper day
oS
imethicone
when necessary
Grade 1 (M
ild)A
symptom
atic; clinical or diagnosticobservation only; intervention not indicated
Grade 2 (M
oderate)A
bdominal pain;blood or m
ucus in stoolG
rade 3 (Severe)Severe abdom
inal pain; change in bow
el habits; medical intervention
indicated; peritonealsigns
Grade 4 (Potentially Life-Threatening)
Life-threatening(e.g., hem
odynamic
collapse); urgent intervention indicated
Grade 5 (D
eath)
Nursing Im
plementation:
-C
ompare baseline assessm
ent:grade & docum
ent bowel frequency
-E
arly identification and evaluation of patient symptom
s-
Grade sym
ptom &
determine level of care and interventions required
-E
arly intervention with lab w
ork and office visit if colitis symptom
s aresuspected
*Steroid
taperinstructions/calendarasa
guidebutnotan
absolute-
Tapershouldconsiderpatient’s
currentsymptom
profile-
Close
follow-up
inperson
orbyphone,based
onindividualneed
&sym
ptomatology
-A
nti-acidtherapy
dailyas
gastriculcerprevention
while
onsteroids
-R
eviewsteroid
medication
sideeffects:m
oodchanges
(anger,reactive,hyperaware,euphoric,m
ania), increasedappetite,interrupted
sleep,oralthrush,fluidretention
-B
ealertto
recurringsym
ptoms
assteroids
taperdown
& reportthem
(tapermay
needto
beadjusted)
Long-term
high-dosesteroids:
-C
onsiderantimicrobialprophylaxis
(sulfamethoxazole/trim
ethoprim double dose M
/W/F; single dose if used
daily) or alternative if sulfa-allergic (e.g., atovaquone [Mepron
®]1500 mg po
daily)-
Consideradditionalantiviraland antifungalcoverage
-A
voidalcohol/acetam
inophenorotherhepatoxins
Grade 1 (M
ild)-
Increase of <4 stools/day over baseline
-M
ild increase in ostomy output
compared w
ithbaseline
Grade 2 (M
oderate)-
Increase of 4–6 stools/day over baseline
-M
oderate increase of output in ostom
y compared w
ithbaseline
Grade 3 (Severe)
-Increase of ≥7 stools/day
over baseline; incontinence
-H
ospitalization indicated-
Severe increase in ostom
y output com
pared with
baseline-
Limiting self-care A
DLs
Grade 4 (Potentially Life-Threatening)
-Life-threatening
(e.g., perforation, bleeding, ischem
ic necrosis, toxic megacolon)
-U
rgent intervention required
Grade 5 (D
eath)
RED FLAGS:
-Change in gastrointestinal function, decreased appetite
-Bloating, nausea
-M
ore frequent stools, consistency change from loose to liquid
-Abdom
inal pain -
Fever
AD
Ls = activities of daily living; PD
-1=
programm
ed cell death protein 1
Copyright ©
2017 Melanom
a Nursing Initiative.
© 2017 The M
elanoma N
ursing Initiative. All rights reserved
ww
w.them
elanomanurse.org
Gastrointestinal Toxicity Page 3 of 3
© 2017 The M
elanoma N
ursing Initiative. All rights reserved
ww
w.them
elanomanurse.org
Mucositis Xerostom
ia Page 1 of 2
Care Step Pathw
ay-M
ucositis & Xerostom
ia
Nursing Assessm
entLook:-
Does the patient appear uncom
fortable?-
Does the patient appear unw
ell?-
Difficulty talking?
-Licking lips to m
oisten often?-
Weight loss?
-D
oes the patient appear dehydrated?-
Does the patient have thrush?
Grading Toxicity
Oral M
ucositisD
efinition: A disorder characterized by inflamm
ation of the oral mucosa
Xerostom
ia (dry mouth)
Definition: A disorder characterized by reduced salivary flow
in the oralregion
Listen:-
Does the patient report?o
Mouth pain (tongue, gum
s, buccal mucosa)
oM
outh sores o
Difficulty eating
oW
aking during the sleep to sip water
oR
ecent dental-related issueso
Need for dental w
ork (e.g., root canal, tooth extraction)
-H
ave symptom
s worsened?
Recognize:
-A
history of mouth sores
-D
oes patient smoke?
-C
oncomitant m
edications associated with causing
dry mouth?
-R
eports of dry mouth often accom
pany mucositis
-O
ther reports of dry mem
branes(e.g., eyes, nasal
passages, vagina)
Managem
ent(Including anticipatory guidance)
Overall Strategy
-Assess for other etiology of m
ucositis or dry mouth: candidiasis;ask patient about new
medications (particularly antihistam
ines), herbals, supplements,
alternative/complem
entary therapies
Grade 1 (M
ild)-
Anticipate im
munotherapy to continue
-A
dvise ongoing basic oral hygiene A
dvise avoidance of hot, spicy, acidic foods
-A
nticipate possible alternative treatm
ent(s)o
Zinc supplements or 0.2%
zinc sulfate m
outhwash
oP
robiotics with Lactobacillus
oB
enzydamine
HC
I-
Assess patient &
family
understanding of recomm
endations and rationaleo
Identify barriers to adherence
Grade 2 (M
oderate)-
Ipilimum
ab to be withheld for any G
rade 2event (resum
e when G
rade 0/1)-
Imm
unotherapy to be discontinued for Grade
2events persisting ≥6
(ipilimum
ab)or ≥12 weeks
(pembrolizum
ab, nivolumab)
-A
ssess for Sicca syndrom
e, Sjӧgren’s syndrom
e -
Encourage vigilant oral hygiene
Xerostomia:
-A
dvise moistening agents
oS
aliva substituteo
Synthetic saliva
oO
ral lubricants -
Advise secretagogues o
Nonpharm
acologic
Sugarless gum
S
ugarless hard candies
Natural lem
ono
Pharm
acologic
Pilocarpine
C
evimeline H
CI
Mucositis:
-V
igilant oral hygieneo
Increase frequency of brushing to Q4
hours and at bedtime
oIf unable to tolerate brushing, advise chlorhexidine gluconate 0.12%
or sodium
bicarbonate rinses
1 tsp baking soda in 8 ounces of water
or
½ tsp salt and 2 tbsp
sodium
bicarbonate dissolved in 4 cups of w
ater-
Encourage sips of cool w
ater or crushed ice o
Encourage soft, bland non-acidic foods
oA
nticipatory guidance regarding use of pharm
acologic agents (as applicable)
Analgesics
Gelclair®
, Zilactin®
2%
viscous lidocaine applied to lesions 15 m
inutes prior to meals
2%
morphine m
outhwash
0.5%
doxepin mouthw
ash
“Miracle M
outhwash”:
diphenhydramine/lidocaine/
simethicone
C
orticosteroid rinses
Dexam
ethasone oral solutiono
Monitor w
eighto
Monitor hydration status
-N
utrition referral if appropriate
Grades 3-4 (Severe or Life-Threatening)
-N
ivolumab to be w
ithheld for first occurrence G
rade 3 event. Imm
unotherapyto be
discontinuedfor any G
rade 4 event or for aG
rade 3 event persisting ≥12 weeks
(ipilimum
ab, pembrolizum
ab, nivolumab)or any
recurrent Grade 3 event (pem
brolizumab,
nivolumab)
-A
nticipate hospitalization if unable to tolerate oral solids orliquids
-U
nclear role of systemic corticosteroids
-A
nticipate need for supplemental nutrition
oE
nteral o
Parenteral
-A
nticipatory guidance regarding use of pharm
acologic agents o
Analgesics
System
ic opioids may be indicated
-O
ral care -
Assess patient &
family understanding of toxicity
and rationale for interventions as well as
treatment discontinuation
oIdentify barriers to adherence
Grade 1 (M
ild)A
symptom
atic or mild sym
ptoms;
intervention not indicated
Grade 2 (M
oderate)M
oderate pain; not interfering w
ith oral intake; modified diet
indicated
Grade 3 (Severe)
Severe pain; interfering w
ith oral intake
Grade 4 (Potentially Life-Threatening)
Life-threatening consequences; urgent intervention indicated
Grade 5
(Death)
Grade 1 (M
ild)S
ymptom
atic (e.g.,dry or thick saliva) w
ithout significant dietary alteration; unstim
ulated saliva flow
>0.2 mL/m
in
Grade 2 (M
oderate)M
oderate symptom
s; oral intake alterations (e.g., copious w
ater, other lubricants, diet lim
ited to purees and/or soft, m
oist foods); unstim
ulated saliva 0.1 to 0.2 m
L/min
Grade 3 (Severe)
Inability to adequately aliment
orally; tube feeding or total parenteral nutrition
indicated; unstim
ulated saliva <0.1 mL/m
in
Grade 4 (Potentially Life-Threatening)
Life-threatening consequences; urgent intervention indicated
Grade 5
(Death)
Interventions in at-risk patients-
Advise basic oral hygiene:o
Tooth brushing (soft toothbrush, avoid toothpaste w
ith whitening
agents) o
Use of dental floss daily
o>1 m
outh rinses to maintain oral
hygiene (avoid comm
ercial m
outhwashes or those w
ith alcohol)
-If patient w
ears dentures, assess for proper fit, areas of irritation, etc.
-D
ental referral if necessary -
Assess patient &
family
understanding of prevention strategies and rationaleo
Identify barriers to adherence
Copyright ©
2017 Melanom
a Nursing Initiative.
© 2017 The M
elanoma N
ursing Initiative. All rights reserved
ww
w.them
elanomanurse.org
Care Step Pathw
ay-M
ucositis & Xerostom
ia
Nursing Assessm
entLook:-
Does the patient appear uncom
fortable?-
Does the patient appear unw
ell?-
Difficulty talking?
-Licking lips to m
oisten often?-
Weight loss?
-D
oes the patient appear dehydrated?-
Does the patient have thrush?
Grading Toxicity
Oral M
ucositisD
efinition: A disorder characterized by inflamm
ation of the oral mucosa
Xerostom
ia (dry mouth)
Definition: A disorder characterized by reduced salivary flow
in the oralregion
Listen:-
Does the patient report?o
Mouth pain (tongue, gum
s, buccal mucosa)
oM
outh sores o
Difficulty eating
oW
aking during the sleep to sip water
oR
ecent dental-related issueso
Need for dental w
ork (e.g., root canal, tooth extraction)
-H
ave symptom
s worsened?
Recognize:
-A
history of mouth sores
-D
oes patient smoke?
-C
oncomitant m
edications associated with causing
dry mouth?
-R
eports of dry mouth often accom
pany mucositis
-O
ther reports of dry mem
branes(e.g., eyes, nasal
passages, vagina)
Managem
ent(Including anticipatory guidance)
Overall Strategy
-Assess for other etiology of m
ucositis or dry mouth: candidiasis;ask patient about new
medications (particularly antihistam
ines), herbals, supplements,
alternative/complem
entary therapies
Grade 1 (M
ild)-
Anticipate im
munotherapy to continue
-A
dvise ongoing basic oral hygiene A
dvise avoidance of hot, spicy, acidic foods
-A
nticipate possible alternative treatm
ent(s)o
Zinc supplements or 0.2%
zinc sulfate m
outhwash
oP
robiotics with Lactobacillus
oB
enzydamine
HC
I-
Assess patient &
family
understanding of recomm
endations and rationaleo
Identify barriers to adherence
Grade 2 (M
oderate)-
Ipilimum
ab to be withheld for any G
rade 2event (resum
e when G
rade 0/1)-
Imm
unotherapy to be discontinued for Grade
2events persisting ≥6
(ipilimum
ab)or ≥12 weeks
(pembrolizum
ab, nivolumab)
-A
ssess for Sicca syndrom
e, Sjӧgren’s syndrom
e -
Encourage vigilant oral hygiene
Xerostomia:
-A
dvise moistening agents
oS
aliva substituteo
Synthetic saliva
oO
ral lubricants -
Advise secretagogues o
Nonpharm
acologic
Sugarless gum
S
ugarless hard candies
Natural lem
ono
Pharm
acologic
Pilocarpine
C
evimeline H
CI
Mucositis:
-V
igilant oral hygieneo
Increase frequency of brushing to Q4
hours and at bedtime
oIf unable to tolerate brushing, advise chlorhexidine gluconate 0.12%
or sodium
bicarbonate rinses
1 tsp baking soda in 8 ounces of water
or
½ tsp salt and 2 tbsp
sodium
bicarbonate dissolved in 4 cups of w
ater-
Encourage sips of cool w
ater or crushed ice o
Encourage soft, bland non-acidic foods
oA
nticipatory guidance regarding use of pharm
acologic agents (as applicable)
Analgesics
Gelclair®
, Zilactin®
2%
viscous lidocaine applied to lesions 15 m
inutes prior to meals
2%
morphine m
outhwash
0.5%
doxepin mouthw
ash
“Miracle M
outhwash”:
diphenhydramine/lidocaine/
simethicone
C
orticosteroid rinses
Dexam
ethasone oral solutiono
Monitor w
eighto
Monitor hydration status
-N
utrition referral if appropriate
Grades 3-4 (Severe or Life-Threatening)
-N
ivolumab to be w
ithheld for first occurrence G
rade 3 event. Imm
unotherapyto be
discontinuedfor any G
rade 4 event or for aG
rade 3 event persisting ≥12 weeks
(ipilimum
ab, pembrolizum
ab, nivolumab)or any
recurrent Grade 3 event (pem
brolizumab,
nivolumab)
-A
nticipate hospitalization if unable to tolerate oral solids orliquids
-U
nclear role of systemic corticosteroids
-A
nticipate need for supplemental nutrition
oE
nteral o
Parenteral
-A
nticipatory guidance regarding use of pharm
acologic agents o
Analgesics
System
ic opioids may be indicated
-O
ral care -
Assess patient &
family understanding of toxicity
and rationale for interventions as well as
treatment discontinuation
oIdentify barriers to adherence
Grade 1 (M
ild)A
symptom
atic or mild sym
ptoms;
intervention not indicated
Grade 2 (M
oderate)M
oderate pain; not interfering w
ith oral intake; modified diet
indicated
Grade 3 (Severe)
Severe pain; interfering w
ith oral intake
Grade 4 (Potentially Life-Threatening)
Life-threatening consequences; urgent intervention indicated
Grade 5
(Death)
Grade 1 (M
ild)S
ymptom
atic (e.g.,dry or thick saliva) w
ithout significant dietary alteration; unstim
ulated saliva flow
>0.2 mL/m
in
Grade 2 (M
oderate)M
oderate symptom
s; oral intake alterations (e.g., copious w
ater, other lubricants, diet lim
ited to purees and/or soft, m
oist foods); unstim
ulated saliva 0.1 to 0.2 m
L/min
Grade 3 (Severe)
Inability to adequately aliment
orally; tube feeding or total parenteral nutrition
indicated; unstim
ulated saliva <0.1 mL/m
in
Grade 4 (Potentially Life-Threatening)
Life-threatening consequences; urgent intervention indicated
Grade 5
(Death)
Interventions in at-risk patients-
Advise basic oral hygiene:o
Tooth brushing (soft toothbrush, avoid toothpaste w
ith whitening
agents) o
Use of dental floss daily
o>1 m
outh rinses to maintain oral
hygiene (avoid comm
ercial m
outhwashes or those w
ith alcohol)
-If patient w
ears dentures, assess for proper fit, areas of irritation, etc.
-D
ental referral if necessary -
Assess patient &
family
understanding of prevention strategies and rationaleo
Identify barriers to adherence
Copyright ©
2017 Melanom
a Nursing Initiative.
Mucositis Xerostom
ia Page 2 of 2
© 2017 The M
elanoma N
ursing Initiative. All rights reserved
ww
w.them
elanomanurse.org
Hepatotoxicity Page 1 of 3
RED FLAGS:
- Severe abdom
inal pain, ascites, somnolence, jaundice, m
ental status changes
Care Step Pathw
ay–
Hepatotoxicity
(imm
unotherapy-induced inflamm
ation of liver tissue)
Nursing Assessm
entLook:-
Does the patient appear fatigued or listless?
-D
oes the patient appear jaundiced?-
Does the patient appear diaphoretic?
-D
oes the patient have any ascites?
Grading Toxicity: U
LN
Listen:-
Change in energy level?
-C
hange in skin color? Yellowing?
-C
hange in stool color (paler)?-
Change in urine color (darker/tea colored)?
-A
bdominal pain:specifically, right upper quadrant pain?
-B
ruising or bleeding more easily?
-Fevers?
-C
hange in mental status?
-Increased sw
eating?
Recognize:
-E
levation in LFTso
AS
T/SG
OT
oA
LT/SG
PT
oB
ilirubin (total/direct)-
Alteration in G
I function-
Sym
ptoms such as abdom
inal pain, ascites, som
nolence, and jaundice-
Other potential causes (viral, drug toxicity,
disease progression)
Managem
ent(including anticipatory guidance)
Overall Strategy:
-LFTs should be checked and results review
ed prior to each dose of imm
unotherapy-
Rule out infectious, non-infectious,and m
alignant causes. Consider assessing for new
onset or re-activation of viral hepatitis, medications (acetam
inophen, statins, and
other hepatotoxic meds, or supplem
ents/herbals), recreational substances (alcohol);consider disease progression
Infliximab infusions are notrecom
mended due to potential hepatotoxic effects
Grade 1 (M
ild)A
ST/A
LT:>U
LN–
3.0×U
LNB
ilirubin: >ULN
–1.5×
ULN
Grade 2 (M
oderate)A
ST/A
LT:>3.0×
–5.0×
ULN
Bilirubin: >1.5×
–3.0×
ULN
Grade 3 (Severe)
AS
T/ALT: >5.0×
–20.0×
ULN
Bilirubin: >3.0 ×
ULN
Grade 4 (Potentially Life-Threatening)
AS
T/ALT: >20×
ULN
Bilirubin: >10 ×
ULN
Grade 5 (D
eath)
Grade 1 (M
ild)-
Imm
unotherapy may be
withheld if LFTs are trending
upward; recheck LFTs w
ithin ~ 1 w
eek
Grade 3 (Severe)
-S
teroids*to be initiated at 2
mg/kg/day
prednisone or equivalent daily oral -
Nivolum
abto be w
ithheldfor first-occurrence
Grade 3 event. Ipilim
umab to be discontinued
for any Grade 3 event, and nivolum
ab or pem
brolizumab
for any recurrent Grade 3 event
or Grade 3 event persisting ≥12 w
eeks-
Adm
ission for IV steroids*
-R
/O hepatitis infection (acute infection or
reactivation)-
Daily LFTs
-If sustained elevation is significant and/or refractory to steroids* potential forA
DD
ING
to steroid regim
en imm
unosuppressive agent:o
CellC
ept ®(m
ycophenolate mofetil) 500
mg
-1000
mg po q 12 hours
OR
oA
ntithymocyte globulin infusion
-H
epatology/gastroenterology consult-
Consider liver biopsy
-If LFTs stable/declining daily for 5 consecutive days: decrease LFT checks to q
3 days, then w
eekly-
If LFTnorm
alized and symptom
s resolved,steroids* to be tapered over ≥4 w
eeks
Grade 4 (Life-Threatening)
-Im
munotherapy
to be discontinued-
Hospital adm
ission-
Steroids*
to be initiated at2m
g/kg/day prednisone or equivalent daily intravenous
-R
/O hepatitis infection
-D
aily LFTs-
If sustained elevation and refractory to steroids* potential for A
DD
ING
to steroid regim
en:o
CellC
ept ®(m
ycophenolate mofetil) 500
mg
-1000m
g po or IV q 12 hours
OR
oA
ntithymocyte globulin infusion
-H
epatology/gastroenterology consult-
Consider liver biopsy
-If LFTs stable/declining daily for 5 consecutive days: decrease LFT checks to q
3 days, then weekly
-If LFTs norm
alized and symptom
s resolved,steroids*to be tapered
slowly over ≥4
weeks
Nursing Im
plementation:
-R
eview LFT
results prior to administration of im
munotherapy
-E
arly identification and evaluation of patient symptom
s-
Early intervention w
ith lab work and office visit if hepatotoxicity is suspected
-G
rade LFTsand
any other accompanying sym
ptoms
*Steroid
taperinstructions/calendarasa
guidebutnotan
absolute-
Tapershouldconsiderpatient’s
currentsymptom
profile-
Close
follow-up
inperson
orbyphone,based
onindividualneed
&sym
ptomatology
-A
nti-acidtherapy
dailyas
gastriculcerprevention
while
onsteroids
-R
eviewsteroid
medication
sideeffects:m
oodchanges
(anger,reactive,hyperaware,euphoric,m
ania), increasedappetite,interrupted
sleep,oralthrush,fluidretention
-B
ealertto
recurringsym
ptoms
assteroids
taperdown
& reportthem
(tapermay
needto
beadjusted)
Long-term
high-dosesteroids:
-C
onsiderantimicrobialprophylaxis
(sulfamethoxazole/trim
ethoprim double dose M
/W/F; single dose if used
daily) or alternative if sulfa-allergic (e.g., atovaquone [Mepron
®]1500 mg po daily)
-C
onsideradditionalantiviraland antifu ngalcoverage-
Avoid
alcohol/acetaminophen
orotherhepatoxins
Grade 2 (M
oderate)-
Imm
unotherapyto be w
ithheld; recheck LFTs daily x 3 days or every 3 days;to be resum
edw
hen complete/partial resolution
of adverse reaction (Grade 0/1)
-Im
munotherapy to be discontinued for
Grade 2 events lasting ≥6
(ipilimum
ab) or ≥12
weeks
(pembrolizum
ab, nivolumab),
orforinability to reduce steroid dose to 7.5 m
g prednisone or equivalent per day -
Consider starting steroids* 0.5
mg
–1
mg/kg/day prednisone or equivalent daily
(IV m
ethylprednisolone 125m
g total daily dose) +
an anti-acid-
Considerhospitaladm
ission for IV
steroids*-
If LFT normalized and sym
ptoms
resolved, steroids*to be tapered
over ≥ 4 w
eeksw
hen function recovers-
Once patientreturns to baseline or G
rade 0-1,consider resum
ing treatment
ALT
=alanine am
inotransferase; AS
T=
aspartate aminotransferase; G
I=gastrointestinal;LFT
-liver function test; SG
OT
-serum glutam
ic oxaloacetic transaminase; S
GP
T=
serum glutam
ic pyruvic transam
inase; ULN
=upper lim
it of normal
Copyright ©
2017 Melanom
a Nursing Initiative.
© 2017 The M
elanoma N
ursing Initiative. All rights reserved
ww
w.them
elanomanurse.org
Hepatotoxicity Page 2 of 3
RED FLAGS:
- Severe abdom
inal pain, ascites, somnolence, jaundice, m
ental status changes
Care Step Pathw
ay–
Hepatotoxicity
(imm
unotherapy-induced inflamm
ation of liver tissue)
Nursing Assessm
entLook:-
Does the patient appear fatigued or listless?
-D
oes the patient appear jaundiced?-
Does the patient appear diaphoretic?
-D
oes the patient have any ascites?
Grading Toxicity: U
LN
Listen:-
Change in energy level?
-C
hange in skin color? Yellowing?
-C
hange in stool color (paler)?-
Change in urine color (darker/tea colored)?
-A
bdominal pain:specifically, right upper quadrant pain?
-B
ruising or bleeding more easily?
-Fevers?
-C
hange in mental status?
-Increased sw
eating?
Recognize:
-E
levation in LFTso
AS
T/SG
OT
oA
LT/SG
PT
oB
ilirubin (total/direct)-
Alteration in G
I function-
Sym
ptoms such as abdom
inal pain, ascites, som
nolence, and jaundice-
Other potential causes (viral, drug toxicity,
disease progression)
Managem
ent(including anticipatory guidance)
Overall Strategy:
-LFTs should be checked and results review
ed prior to each dose of imm
unotherapy-
Rule out infectious, non-infectious,and m
alignant causes. Consider assessing for new
onset or re-activation of viral hepatitis, medications (acetam
inophen, statins, and
other hepatotoxic meds, or supplem
ents/herbals), recreational substances (alcohol);consider disease progression
Infliximab infusions are notrecom
mended due to potential hepatotoxic effects
Grade 1 (M
ild)A
ST/A
LT:>U
LN–
3.0×U
LNB
ilirubin: >ULN
–1.5×
ULN
Grade 2 (M
oderate)A
ST/A
LT:>3.0×
–5.0×
ULN
Bilirubin: >1.5×
–3.0×
ULN
Grade 3 (Severe)
AS
T/ALT: >5.0×
–20.0×
ULN
Bilirubin: >3.0 ×
ULN
Grade 4 (Potentially Life-Threatening)
AS
T/ALT: >20×
ULN
Bilirubin: >10 ×
ULN
Grade 5 (D
eath)
Grade 1 (M
ild)-
Imm
unotherapy may be
withheld if LFTs are trending
upward; recheck LFTs w
ithin ~ 1 w
eek
Grade 3 (Severe)
-S
teroids*to be initiated at 2
mg/kg/day
prednisone or equivalent daily oral -
Nivolum
abto be w
ithheldfor first-occurrence
Grade 3 event. Ipilim
umab to be discontinued
for any Grade 3 event, and nivolum
ab or pem
brolizumab
for any recurrent Grade 3 event
or Grade 3 event persisting ≥12 w
eeks-
Adm
ission for IV steroids*
-R
/O hepatitis infection (acute infection or
reactivation)-
Daily LFTs
-If sustained elevation is significant and/or refractory to steroids* potential forA
DD
ING
to steroid regim
en imm
unosuppressive agent:o
CellC
ept ®(m
ycophenolate mofetil) 500
mg
-1000
mg po q 12 hours
OR
oA
ntithymocyte globulin infusion
-H
epatology/gastroenterology consult-
Consider liver biopsy
-If LFTs stable/declining daily for 5 consecutive days: decrease LFT checks to q
3 days, then w
eekly-
If LFTnorm
alized and symptom
s resolved,steroids* to be tapered over ≥4 w
eeks
Grade 4 (Life-Threatening)
-Im
munotherapy
to be discontinued-
Hospital adm
ission-
Steroids*
to be initiated at2m
g/kg/day prednisone or equivalent daily intravenous
-R
/O hepatitis infection
-D
aily LFTs-
If sustained elevation and refractory to steroids* potential for A
DD
ING
to steroid regim
en:o
CellC
ept ®(m
ycophenolate mofetil) 500
mg
-1000m
g po or IV q 12 hours
OR
oA
ntithymocyte globulin infusion
-H
epatology/gastroenterology consult-
Consider liver biopsy
-If LFTs stable/declining daily for 5 consecutive days: decrease LFT checks to q
3 days, then weekly
-If LFTs norm
alized and symptom
s resolved,steroids*to be tapered
slowly over ≥4
weeks
Nursing Im
plementation:
-R
eview LFT
results prior to administration of im
munotherapy
-E
arly identification and evaluation of patient symptom
s-
Early intervention w
ith lab work and office visit if hepatotoxicity is suspected
-G
rade LFTsand
any other accompanying sym
ptoms
*Steroid
taperinstructions/calendarasa
guidebutnotan
absolute-
Tapershouldconsiderpatient’s
currentsymptom
profile-
Close
follow-up
inperson
orbyphone,based
onindividualneed
&sym
ptomatology
-A
nti-acidtherapy
dailyas
gastriculcerprevention
while
onsteroids
-R
eviewsteroid
medication
sideeffects:m
oodchanges
(anger,reactive,hyperaware,euphoric,m
ania), increasedappetite,interrupted
sleep,oralthrush,fluidretention
-B
ealertto
recurringsym
ptoms
assteroids
taperdown
& reportthem
(tapermay
needto
beadjusted)
Long-term
high-dosesteroids:
-C
onsiderantimicrobialprophylaxis
(sulfamethoxazole/trim
ethoprim double dose M
/W/F; single dose if used
daily) or alternative if sulfa-allergic (e.g., atovaquone [Mepron
®]1500 mg po daily)
-C
onsideradditionalantiviraland antifu ngalcoverage-
Avoid
alcohol/acetaminophen
orotherhepatoxins
Grade 2 (M
oderate)-
Imm
unotherapyto be w
ithheld; recheck LFTs daily x 3 days or every 3 days;to be resum
edw
hen complete/partial resolution
of adverse reaction (Grade 0/1)
-Im
munotherapy to be discontinued for
Grade 2 events lasting ≥6
(ipilimum
ab) or ≥12
weeks
(pembrolizum
ab, nivolumab),
orforinability to reduce steroid dose to 7.5 m
g prednisone or equivalent per day -
Consider starting steroids* 0.5
mg
–1
mg/kg/day prednisone or equivalent daily
(IV m
ethylprednisolone 125m
g total daily dose) +
an anti-acid-
Considerhospitaladm
ission for IV
steroids*-
If LFT normalized and sym
ptoms
resolved, steroids*to be tapered
over ≥ 4 w
eeksw
hen function recovers-
Once patientreturns to baseline or G
rade 0-1,consider resum
ing treatment
ALT
=alanine am
inotransferase; AS
T=
aspartate aminotransferase; G
I=gastrointestinal;LFT
-liver function test; SG
OT
-serum glutam
ic oxaloacetic transaminase; S
GP
T=
serum glutam
ic pyruvic transam
inase; ULN
=upper lim
it of normal
Copyright ©
2017 Melanom
a Nursing Initiative.
© 2017 The M
elanoma N
ursing Initiative. All rights reserved
ww
w.them
elanomanurse.org
Hepatotoxicity Page 3 of 3
RED FLAGS:
- Severe abdom
inal pain, ascites, somnolence, jaundice, m
ental status changes
Care Step Pathw
ay–
Hepatotoxicity
(imm
unotherapy-induced inflamm
ation of liver tissue)
Nursing Assessm
entLook:-
Does the patient appear fatigued or listless?
-D
oes the patient appear jaundiced?-
Does the patient appear diaphoretic?
-D
oes the patient have any ascites?
Grading Toxicity: U
LN
Listen:-
Change in energy level?
-C
hange in skin color? Yellowing?
-C
hange in stool color (paler)?-
Change in urine color (darker/tea colored)?
-A
bdominal pain:specifically, right upper quadrant pain?
-B
ruising or bleeding more easily?
-Fevers?
-C
hange in mental status?
-Increased sw
eating?
Recognize:
-E
levation in LFTso
AS
T/SG
OT
oA
LT/SG
PT
oB
ilirubin (total/direct)-
Alteration in G
I function-
Sym
ptoms such as abdom
inal pain, ascites, som
nolence, and jaundice-
Other potential causes (viral, drug toxicity,
disease progression)
Managem
ent(including anticipatory guidance)
Overall Strategy:
-LFTs should be checked and results review
ed prior to each dose of imm
unotherapy-
Rule out infectious, non-infectious,and m
alignant causes. Consider assessing for new
onset or re-activation of viral hepatitis, medications (acetam
inophen, statins, and
other hepatotoxic meds, or supplem
ents/herbals), recreational substances (alcohol);consider disease progression
Infliximab infusions are notrecom
mended due to potential hepatotoxic effects
Grade 1 (M
ild)A
ST/A
LT:>U
LN–
3.0×U
LNB
ilirubin: >ULN
–1.5×
ULN
Grade 2 (M
oderate)A
ST/A
LT:>3.0×
–5.0×
ULN
Bilirubin: >1.5×
–3.0×
ULN
Grade 3 (Severe)
AS
T/ALT: >5.0×
–20.0×
ULN
Bilirubin: >3.0 ×
ULN
Grade 4 (Potentially Life-Threatening)
AS
T/ALT: >20×
ULN
Bilirubin: >10 ×
ULN
Grade 5 (D
eath)
Grade 1 (M
ild)-
Imm
unotherapy may be
withheld if LFTs are trending
upward; recheck LFTs w
ithin ~ 1 w
eek
Grade 3 (Severe)
-S
teroids*to be initiated at 2
mg/kg/day
prednisone or equivalent daily oral -
Nivolum
abto be w
ithheldfor first-occurrence
Grade 3 event. Ipilim
umab to be discontinued
for any Grade 3 event, and nivolum
ab or pem
brolizumab
for any recurrent Grade 3 event
or Grade 3 event persisting ≥12 w
eeks-
Adm
ission for IV steroids*
-R
/O hepatitis infection (acute infection or
reactivation)-
Daily LFTs
-If sustained elevation is significant and/or refractory to steroids* potential forA
DD
ING
to steroid regim
en imm
unosuppressive agent:o
CellC
ept ®(m
ycophenolate mofetil) 500
mg
-1000
mg po q 12 hours
OR
oA
ntithymocyte globulin infusion
-H
epatology/gastroenterology consult-
Consider liver biopsy
-If LFTs stable/declining daily for 5 consecutive days: decrease LFT checks to q
3 days, then w
eekly-
If LFTnorm
alized and symptom
s resolved,steroids* to be tapered over ≥4 w
eeks
Grade 4 (Life-Threatening)
-Im
munotherapy
to be discontinued-
Hospital adm
ission-
Steroids*
to be initiated at2m
g/kg/day prednisone or equivalent daily intravenous
-R
/O hepatitis infection
-D
aily LFTs-
If sustained elevation and refractory to steroids* potential for A
DD
ING
to steroid regim
en:o
CellC
ept ®(m
ycophenolate mofetil) 500
mg
-1000m
g po or IV q 12 hours
OR
oA
ntithymocyte globulin infusion
-H
epatology/gastroenterology consult-
Consider liver biopsy
-If LFTs stable/declining daily for 5 consecutive days: decrease LFT checks to q
3 days, then weekly
-If LFTs norm
alized and symptom
s resolved,steroids*to be tapered
slowly over ≥4
weeks
Nursing Im
plementation:
-R
eview LFT
results prior to administration of im
munotherapy
-E
arly identification and evaluation of patient symptom
s-
Early intervention w
ith lab work and office visit if hepatotoxicity is suspected
-G
rade LFTsand
any other accompanying sym
ptoms
*Steroid
taperinstructions/calendarasa
guidebutnotan
absolute-
Tapershouldconsiderpatient’s
currentsymptom
profile-
Close
follow-up
inperson
orbyphone,based
onindividualneed
&sym
ptomatology
-A
nti-acidtherapy
dailyas
gastriculcerprevention
while
onsteroids
-R
eviewsteroid
medication
sideeffects:m
oodchanges
(anger,reactive,hyperaware,euphoric,m
ania), increasedappetite,interrupted
sleep,oralthrush,fluidretention
-B
ealertto
recurringsym
ptoms
assteroids
taperdown
& reportthem
(tapermay
needto
beadjusted)
Long-term
high-dosesteroids:
-C
onsiderantimicrobialprophylaxis
(sulfamethoxazole/trim
ethoprim double dose M
/W/F; single dose if used
daily) or alternative if sulfa-allergic (e.g., atovaquone [Mepron
®]1500 mg po daily)
-C
onsideradditionalantiviraland antifungalcoverage-
Avoid
alcohol/acetaminophen
orotherhepatoxins
Grade 2 (M
oderate)-
Imm
unotherapyto be w
ithheld; recheck LFTs daily x 3 days or every 3 days;to be resum
edw
hen complete/partial resolution
of adverse reaction (Grade 0/1)
-Im
munotherapy to be discontinued for
Grade 2 events lasting ≥6
(ipilimum
ab) or ≥12
weeks
(pembrolizum
ab, nivolumab),
orforinability to reduce steroid dose to 7.5 m
g prednisone or equivalent per day -
Consider starting steroids* 0.5
mg
–1
mg/kg/day prednisone or equivalent daily
(IV m
ethylprednisolone 125m
g total daily dose) +
an anti-acid-
Considerhospitaladm
ission for IV
steroids*-
If LFT normalized and sym
ptoms
resolved, steroids*to be tapered
over ≥ 4 w
eeksw
hen function recovers-
Once patientreturns to baseline or G
rade 0-1,consider resum
ing treatment
ALT
=alanine am
inotransferase; AS
T=
aspartate aminotransferase; G
I=gastrointestinal;LFT
-liver function test; SG
OT
-serum glutam
ic oxaloacetic transaminase; S
GP
T=
serum glutam
ic pyruvic transam
inase; ULN
=upper lim
it of normal
Copyright ©
2017 Melanom
a Nursing Initiative.
© 2017 The M
elanoma N
ursing Initiative. All rights reserved
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elanomanurse.org
Hypophysitis Page 1 of 2
Nursing Assessm
ent
Care Step Pathw
ay –H
ypophysitis(inflam
mation of the pituitary gland)
Look:-
Does the patient appear fatigued?
-D
oes the patient look listless?-
Does the patient look ill?
-D
oes the patient look uncomfortable?
Grading Toxicity (O
verall)
Listen:-
Does the patient report:o
Change in energy?
oH
eadache?o
Dizziness?
oN
ausea/vomiting?
oA
ltered mental status?
oV
isual disturbances?o
Fever?
Recognize:
-Low
levels of hormones produced by pituitary gland
( AC
TH, TS
H, FS
H, LH
, GH
, prolactin)-
Brain M
RI w
ith pituitary cuts: enhancement and
s welling of the pituitary gland.
-D
DX adrenal Insufficiency: low
cortisol and highA
CTH
-D
DX prim
ary hypothyroidism: low
free T4 and hi ghTS
H
Managem
ent
Overall Strategy:
-Ipilim
umab to be w
ithheld for any symptom
atic hypophysitis and discontinued for symptom
atic reactions persisting ≥6 weeks or for inability to reduce steroid dose to
≤7.5 mg prednisone or equivalent per day
-N
ivolumab to be w
ithheld for Grade 2/3 hypophysitis and discontinued for G
rade 4 hypophysitis. Pembrolizum
abto be w
ithheld for Grade 2 hypophysitis and w
ithheld ordiscontinued for G
rade 3/4 hypophysitis-
1m
g/kg methylprednisolone (or equivalent) IV to be given daily
oIf given during acute phase, m
ay reverse inflamm
atory process-
To be followed w
ith prednisone 1-2m
g/kg daily with gradual tapering over at least 4 w
eeks-
Long-term supplem
entation of affected hormones is often required
oSecondary hypothyroidism
requiring levothyroxine replacement
oSecondary hypoadrenalism
requiring replacement hydrocortisone
Typical dose: 20 m
g qAM and 10 m
g qPM-
Assess risk of opportunistic infection based on duration of steroid taper (and consider prophylaxis if needed)-
Collaborative m
anagement approach w
ith endocrinology (particularly if permanent loss of organ function)
Grade 1 (M
ild)A
symptom
atic or mild sym
ptoms;
clinical or diagnostic observation only (headache, fatigue)
Grade 2 (M
oderate)M
oderate symptom
s;limiting age-
appropriate instrumental A
DLs
(headache, fatigue)
Grade 3 (Severe)
Severe or m
edically significant sym
ptoms; lim
iting self-care ADL
(sepsis, severe ataxia)
Grade 4 (Potentially Life-Threatening)
Urgent intervention required (sepsis, severe
ataxia)
Grade 5 (D
eath)
Nursing Im
plementation:
-A
CTH
and thyroid panel should be checked at baseline and prior to each dose ofipilimum
ab-
Ensure that M
RI is ordered w
ith pituitary cuts or via pituitaryprotocol
-A
nticipate treatment w
ith corticosteroid and imm
unotherapy hold-
Review
proper administration of steroid
oTake w
ith food o
Take in AM
-E
ducate patient regarding possibility of permanent loss of organ function (pituitary; possibly others
if involved [thyroid, adrenal glands])-
Sick-day instructions, vaccinations,etc
*Steroid
taperinstructions/calendarasa
guidebutnotan
absolute-
Tapershouldconsiderpatient’s
currentsymptom
profile-
Close
follow-up
inperson
orbyphone,based
onindividualneed
&sym
ptomatology
-A
nti-acidtherapy
dailyas
gastriculcerprevention
while
onsteroids
-R
eviewsteroid
medication
sideeffects:m
oodchanges
(anger,reactive,hyperaware,euphoric,m
ania),increasedappetite,interrupted
sleep,oralthrush,fluidretention
-B
ealertto
recurringsym
ptoms
assteroids
taperdown
& reportthem
(tapermay
needto
beadjusted)
Long-termhigh-dose
steroids:-
Considerantim
icrobialprophylaxis(sulfam
ethoxazole/trimethoprim
double dose M/W
/F;single dose ifuseddaily) or alternative ifsulfa-allergic (e.g.,atovaquone [M
epron®]1500 m
g podaily)
-C
onsideradditionalantiviraland antifungalcoverage-
Avoid
alcohol/acetaminophen
orotherhepatoxins
AC
TH = adrenocorticotropic horm
one; AD
Ls = activities ofdaily living; DD
X = differentialdiagnosis; FSH
= follicle-stimulating horm
one; GH
= growth horm
one; LH =
luteinizing hormone; M
RI =
magnetic resonance im
aging;TSH
= thyroid stimulating horm
one.
RED FLAGS:
-Sym
ptoms of adrenal insufficiency
Copyright ©
2017 Melanom
a Nursing Initiative.
© 2017 The M
elanoma N
ursing Initiative. All rights reserved
ww
w.them
elanomanurse.org
Hypophysitis Page 2 of 2
Nursing Assessm
ent
Care Step Pathw
ay–
Hypophysitis
(inflamm
ation of thepituitary
gland)
Look:-
Does the patient appear fatigued?
-D
oes the patient looklistless?
-D
oes the patient lookill?
-D
oes the patient lookuncom
fortable?
Grading Toxicity (O
verall)
Listen:-
Does the patientreport:o
Change in energy?
oH
eadache?o
Dizziness?
oN
ausea/vomiting?
oA
ltered mental status?
oV
isual disturbances?o
Fever?
Recognize:
-Low
levels of hormones produced by pituitary
gland (A
CTH
, TSH
, FSH
, LH, G
H, prolactin)
-B
rain MR
I with pituitary
cuts: enhancementand
swelling of the pituitary gland.
-D
DX adrenal Insufficiency: low
cortisol and high A
CTH
-D
DX prim
ary hypothyroidism: low
free T4 and high TS
H
Managem
ent
Overall Strategy:
-Ipilim
umab to be
withheld for any sym
ptomatic hypophysitis
and discontinued for symptom
atic reactionspersisting ≥6 w
eeks or for inability to reduce steroid dose to≤7.5 m
g prednisone or equivalent per day-
Nivolum
ab to be withheld for G
rade 2/3 hypophysitis and discontinued for Grade 4 hypophysitis.Pem
brolizumab
to be withheld for G
rade 2 hypophysitis and withheld or
discontinued for Grade 3/4 hypophysitis
-1
mg/kg m
ethylprednisolone (or equivalent)IV to be given dailyo
If given during acute phase, may reverse inflam
matory process
-To be follow
ed with
prednisone 1-2m
g/kg dailyw
ith gradual tapering overat least4 weeks
-Long-term
supplementation of affected horm
ones is often requiredo
Secondary hypothyroidismrequiring levothyroxine
replacement
oSecondary
hypoadrenalism requiring replacem
ent hydrocortisone
Typical dose:20 mg qAM
and 10 mg qPM
-Assess risk of opportunistic infection based on duration of steroid taper (and consider prophylaxis if needed)
-C
ollaborative managem
ent approach with endocrinology
(particularly if permanentloss of organ function)
Grade 1 (M
ild)A
symptom
atic or mild
symptom
s;clinical or diagnostic observation only (headache, fatigue)
Grade 2
(Moderate)
Moderate sym
ptoms;lim
iting age-appropriate instrum
ental AD
Ls(headache, fatigue)
Grade 3 (Severe)
Severe or m
edically significantsym
ptoms;lim
iting self-care ADL
(sepsis, severe ataxia)
Grade 4 (Potentially Life-Threatening)
Urgent intervention required (sepsis, severe
ataxia)
Grade 5 (D
eath)
Nursing Im
plementation:
-A
CTH
and thyroid panel should be checked at baseline and prior to each dose of ipilimum
ab-
Ensure that M
RI is ordered w
ith pituitary cuts or via pituitary protocol-
Anticipate treatm
ent with corticosteroid and im
munotherapy hold
-R
eview proper adm
inistration of steroido
Take with food
oTake in A
M-
Educate patient regarding possibility of perm
anent loss of organ function (pituitary; possibly others if involved [thyroid, adrenal glands])-
Sick-day instructions, vaccinations, etc
*Steroid
taperinstructions/calendarasa
guidebutnotan
absolute-
Tapershouldconsiderpatient’s
currentsymptom
profile-
Close
follow-up
inperson
orbyphone,based
onindividualneed
&sym
ptomatology
-A
nti-acidtherapy
dailyas
gastriculcerprevention
while
onsteroids
-R
eviewsteroid
medication
sideeffects:m
oodchanges
(anger,reactive,hyperaware,euphoric,m
ania), increasedappetite,interrupted
sleep,oralthrush,fluidretention
-B
ealertto
recurringsym
ptoms
assteroids
taperdown
& reportthem
(tapermay
needto
beadjusted)
Long-termhigh-dose
steroids:-
Considerantim
icrobialprophylaxis(sulfam
ethoxazole/trimethoprim
double dose M/W
/F; single dose if useddaily) or alternative if sulfa-allergic (e.g., atovaquone [M
epron®]1500 m
g po daily)-
Consideradditionalantiviraland antifungalcoverage
-A
voidalcohol/acetam
inophenorotherhepatoxins
AC
TH = adrenocorticotropic horm
one; AD
Ls = activities of daily living; DD
X = differential diagnosis; FSH
= follicle-stimulating horm
one; GH
= growth horm
one; LH = luteinizing horm
one; MR
I = m
agnetic resonance imaging; TS
H= thyroid stim
ulating hormone.
RED FLAGS:
-Sym
ptoms of adrenal insufficiency
Copyright ©
2017 Melanom
a Nursing Initiative.
© 2017 The M
elanoma N
ursing Initiative. All rights reserved
ww
w.them
elanomanurse.org
Thyroiditis Page 1 of 2
Care Step Pathw
ay –Thyroiditis
(inflamm
ation of the thyroid gland)
Nursing Assessm
entLook:-
Does the patient appear unw
ell?-
Changes in w
eight since last visito
Appear heavier? Thinner?
-C
hanges in hair texture/thickness?-
Appearing hot/cold?
-D
oes the patient look fatigued?
Type of Thyroid Abnorm
ality
Listen:-
Appetite/weight changes?
-H
ot or cold intolerance?-
Change in energy.m
ood, or behavior?-
Palpitations?-
Increased fatigue?-
Bowel-related changes?
oC
onstipation/diarrhea-
Skin-related changes?o
Dry/oily
Recognize:
-E
nsure that patient undergoesthyroid function
testsprior to first dose,every 12 w
eeks while on
PD
-1therapy
and q3 weeks w
ith ipilimum
ab-
High TS
H w
ith low free T4 consistent w
ithprim
ary hypothyroidism-
DD
X: secondary hypothyroidism due t o
hypophysitis, low TS
H and low
free T4-
Occasionally thyroiditis w
ith transienthyperthyroidism
(low TS
H and high free T4)
may be follow
ed by more longstanding
hypothyroidism (high TS
H and low
free T4)-
Other im
mune-related toxicity?
-P
rior thyroid dysfunction?
Managem
ent
TSH>5, <10
mIU
/Lw
ithnorm
al free T4, T3R
epeat TFTs in 4–6 weeks
TSH >10 w
ith normal or low
free T4 & T3
-B
egin thyroid replacement if
symptom
atic-
May consider repeating levels
in 2-4 w
eeks ifasymptom
atic-
Levothyroxine dose 1.6m
cgper
weight (kg)or 75–100
mcg daily
-R
epeat TSH
in 4–6 weeks and
titrate dose to reference rangeTS
H
TSH low
or <0.01 mIU
/Lw
ith high freeT4 or T3-
Considerradioactive iodine therapy
orm
ethimazole treatm
ent-
Consider use of beta blockers
forsym
ptomatic patients (e.g., for tachycardia or
murm
ur)
TSH low
or <0.01 mIU
/Lw
ith norm
al or high free T3 or T4-
Acute thyroiditis
-R
arely Graves’-like disease
TSH>5, <10 m
IU/L
with norm
al free T4, T3S
ubclinical hypothyroidism
TSH >10 m
IU/L
with norm
al or low
free T4 & T3
Prim
ary hypothyroidism
TSH low
or <0.01m
IU/L
with high free T4
or T3H
yperthyroidism
TSH low
or <0.01m
IU/L
with
normal or high free T3 or T4
-C
onsidermeasuring anti-thyroid
antibodies and/or TSH
-receptorautoantibodies (TR
AB
)to establish autoim
mune etiology
-If patienthas not received IV iodinated contrast w
ithin 2 months, can consider
a diagnostic thyroid uptake & scan
-A
cute thyroiditis usually resolves orprogresses to hypothyroidism
;thus,can repeat TFTs in 4–6 w
eeks-
If TRA
B high, obtain a thyroid uptake
scan&
refer to endocrinology-
Short period of 1
mg/kg prednisone or
equivalent may
be helpfulin acute thyroiditis
-C
onsider use of beta blockersand
imm
unotherapyhold forsym
ptomatic
patients(e.g.,beta blockers for
tachycardia/murm
ur and im
munotherapy
holds for patientsw
ho have acute thyroiditis threatening an airw
ay). Therapy is often restarted w
hen symptom
s are mild/tolerable
Nursing Im
plementation:
-Educate patient that hypothyroidism
is generally not reversible-
Assessm
edication compliance w
ith oral thyroid replacement or suppression
-H
istoryof thyroid disorders does not increase ordecrease risk of incidence
-C
onsider collaborative managem
entwith endocrinologist,especially
if the patientis hyperthyroid, particularly if a thyroid scan is needed
RED FLAGS:
-Sw
elling of thyroid gland causingcom
promised airw
ay
DD
X = differentialdiagnosis; PD-1 = program
med celldeath protein 1; TFT = thyroid function test; TS
H = thyroid stim
ulating hormone
Copyright ©
2017 Melanom
a Nursing Initiative.
© 2017 The M
elanoma N
ursing Initiative. All rights reserved
ww
w.them
elanomanurse.org
Thyroiditis Page 2 of 2
Care Step Pathw
ay–
Thyroiditis(inflam
mation of the thyroid gland)
Nursing Assessm
entLook:-
Does the patient appear unw
ell?-
Changes in w
eightsince last visito
Appear heavier? Thinner?
-C
hanges in hair texture/thickness?-
Appearing hot/cold?
-D
oes the patient lookfatigued?
Type of Thyroid Abnorm
ality
Listen:-
Appetite/weightchanges?
-H
ot or cold intolerance?-
Change in energy.m
ood, or behavior?-
Palpitations?-
Increased fatigue?-
Bowel-related changes?
oC
onstipation/diarrhea-
Skin-related changes?o
Dry/oily
Recognize:
-E
nsure thatpatient undergoesthyroid function
testsprior to first dose,every 12 w
eeks while on
PD
-1therapy
and q3 weeks w
ith ipilimum
ab-
High TS
H w
ith low free T4 consistent w
ith prim
ary hypothyroidism-
DD
X: secondary hypothyroidism due to
hypophysitis, low TS
H and low
free T4-
Occasionally thyroiditis w
ith transienthyperthyroidism
(low TS
H and high free T4)
may be follow
ed by more longstanding
hypothyroidism (high TS
H and low
free T4)-
Other im
mune-related toxicity?
-P
rior thyroid dysfunction?
Managem
ent
TSH>5, <10 m
IU/L
with
normal free T4, T3
Repeat TFTs in 4–6 w
eeks
TSH >10 w
ith normal or low
free T4 &
T3-
Begin thyroid replacem
ent ifsym
ptomatic
-M
ay consider repeating levels i n2- 4 w
eeks if asymptom
atic-
Levothyroxine dose 1.6m
cg perw
eight (kg) or 75–100m
cg daily-
Repeat TS
H in 4–6 w
eeks andtitrate dose to reference rangeTS
H
TSH low
or <0.01 mIU
/Lw
ith high free T4 or T3-
Consider radioactive iodine therapy or
methim
azole treatment
-C
onsider use of beta blockers forsym
ptomatic patients (e.g., for tachycardia or
murm
ur)
TSH low
or <0.01 mIU
/Lw
ithnorm
al or high free T3 or T4-
Acute thyroiditis
-R
arely Graves’-like disease
TSH>5, <10
mIU
/Lw
ith normal
free T4, T3S
ubclinical hypothyroidism
TSH >10 m
IU/L
with norm
al or lowfree T4 &
T3P
rimary hypothyroidism
TSH low
or <0.01m
IU/L
with high free T4
or T3H
yperthyroidism
TSH low
or <0.01m
IU/L
with
normal or high free T3 or T4
-C
onsider measuring anti-thyroid
antibodies and/or TSH
-receptorautoantibodies (TR
AB
)to establishautoim
mune etiology
-If patient has not received IV iodinatedc ontrast w
ithin 2 months, can consider
a diagnostic thyroid uptake & scan
-A
cute thyroiditis usually resolves orprogresses to hypothyroidism
; thus,can repeat TFTs in 4–6 w
eeks-
If TRA
B high, obtain a thyroid uptak e
sca n&
refer to endocrinology-
Short period of 1
mg/kg prednisone or
equivalent may be helpful in acute
thyroiditis-
Consider use of beta blockers and
imm
unotherapyhold for sym
ptomatic
patients(e.g.,beta blockers for
tachycardia/murm
ur andim
munotherapy
holds for patientsw
hohave acute thyroiditis threatening anairw
ay). Therapy is often restart edw
hen symptom
s are mild/tolerable
Nursing Im
plementation:
-Educate patient that hypothyroidism
is generally not reversible-
Assess medication com
pliance with oral thyroid replacem
ent or suppression-
History of thyroid disorders does not increase or decrease risk of incidence
-C
onsider collaborative managem
ent with endocrinologist,especially if the patient is hyperthyroid, particularly if a thyroid scan is needed
RED FLAGS:
-Sw
elling of thyroid gland causing comprom
ised airway
DD
X = differential diagnosis; PD-1 = program
med cell death protein 1; TFT = thyroid function test; TS
H = thyroid stim
ulating hormone
Copyright ©
2017 Melanom
a Nursing Initiative.
Care Step Pathw
ay -Type 1 Diabetes
Mellitus
(imm
une destruction of beta cells in pancreas)
Nursing Assessm
ent
Look:-
Does the patient appear fatigued?
-D
oes the patient appear dehydrated?-
Does the breath have a sw
eet/fruity smell?
-Is the patient tachycardic?
Grading Toxicity (B
ased on Fasting Glucose)
Listen:-
Frequent urination?-
Increased thirst?-
Increased hunger?-
Increased fatigue?-
Altered level of consciousness w
ith advanced cases
Recognize:
-S
ymptom
s of diabetes-
Serum
glucose levels-
Other im
mune-related toxicity
-Infections
Managem
entO
verall Strategy: -
Imm
unotherapym
ay be withheld until blood glucose is regulated
-Insulin therapy
-H
ydration-
Endocrine consult
Grade 1 (M
ild)Fasting glucose value >U
LN–
160m
g/dL
Grade 2 (M
oderate)Fasting glucose value >160
–250 m
g/dL
Grade 3 (Severe)
Fasting glucose value >250–
500m
g/dL, hospitalization indicated
Grade 4 (Potentially Life-Threatening)
Fasting glucose value >500 mg/dL, life-
threatening consequences
Grade 5 (D
eath)
Nursing Im
plementation:
-D
iscuss that DM
1 will likely be perm
anent-
Review
signs andsym
ptoms of hyper/hypoglycem
ia-
Follow patients closely w
ith checks on blood glucose levels, fruity breath, and other symptom
s (e.g.,increased infections)-
Assure early intervention
-P
rovide insulin education (orrefer)-
Discuss possibility of other im
mune-related A
Es, including others of endocrine origin
DM
=diabetes m
ellitus;ULN
=upper lim
it of normal
Copyright ©
2017 Melanom
a Nursing Initiative.
© 2017 The M
elanoma N
ursing Initiative. All rights reserved
ww
w.them
elanomanurse.org
Type 1 Diabetes M
ellitus Page 1 of 1
© 2017 The M
elanoma N
ursing Initiative. All rights reserved
ww
w.them
elanomanurse.org
Pneumonitis Page 2 of 2
Care Step Pathw
ay –Pneum
onitis(inflam
mation of lung alveoli)
Nursing Assessm
ent
Look:-
Does the patient appear uncom
fortable?-
Did the patient have difficulty w
alking to the examroom
?O
r going up stairs?-
Does the patient appear short of breath?
-Is the patient tachypneic?
-D
oes the patient appear to be in respiratory distress?
Grading Toxicity
Pneumonitis
Definition: A
disorder characterized by inflamm
ation focally or diffusely affecting the lung parenchyma
H ypoxia D
efinition: A disorder characterized by decrease in the level of oxygen to the body
Listen:-
Has the patient noted any change in breathing?
-D
oes the patient feel short of breath?-
Does the patient note new
dyspnea on exertion?-
Does the patient notice a new
cough? Or a change in an
ex isting cough?-
Have sym
ptoms w
orsened?-
Are sym
ptoms lim
iting AD
Ls?-
Associated sym
ptoms ?
oFatig ue
oW
heezing
Recognize:
-Is the pulse oxim
etry low? Is it low
er than baselineor
compared w
ithlast visit?
Is it low on exertion?
-Is there a pre-existing pulm
onary autoimm
une conditi on(i.e.,sarcoidosis)?
-Is there a history of prior respiratory com
promise
(e.g.,asthm
a, CO
PD
,congestive heart failure)?-
Has the patient experienced other im
mune-related
adverse effects?
Managem
ent
Overall Strategy:
-Assess for other etiologies
such as infection, pulmonary
embolism
, progressive lung metastases,or lung disease
-Early
intervention to maintain orim
prove physical function and impact on Q
OL
-Assess pulse oxim
etry (resting & on exertion)at baseline and at each visit to assist in identifying a decrease at earlyonset.
Grade 1 (M
ild)-
Anticipate im
munotherapy to continue
-C
ontinue to monitor via radiology
testing(q 2–4
weeks, as needed)
-R
eview sym
ptoms to w
atch for with
patient and family,and rem
ember to
assess atevery subsequent visit
Grade 2 (M
oderate)-
Imm
unotherapyto be w
ithheldfor G
rade 2events (resum
e when G
rade 0/1)-
Imm
unotherapyto
be discontinued forrecurrent (pem
brolizumab, nivolum
ab) orpersistent G
rade 2 events (ipilimum
ab,pem
brolizumab, nivolum
ab)-
Anticipate treatm
ent with:
oC
orticosteroids(e.g.,prednisone 1–2
mg/kg/day
or equivalent)until sym
ptoms
improve to baseline,and
then slowtaper overat least1
month
oIf sym
ptoms do not im
prove within 48–
72 hours, corticosteroiddose w
illbe escalated. IV corticosteroids m
aybe
consideredo
Additional supportive care m
edicationsm
ay also be initiated -
Anticipatory guidance on proper
administration
-A
nticipate the use ofempiric antibiotics until
infection is excluded-
Anticipate that bronchoscopy m
aybe
ordered by provider-
Assess
patient &fam
ily understanding ofrecom
mendations and rationale
-Identify barriers to adherence
Grades 3–4 (Severe or Life-Threatening)
-D
iscontinue imm
unotherapy for Grade 3/4
events-
Patient w
ill likely need to be admitted to the
hospital for furthermanagem
ent andsupportive care
-A
nticipate the use ofhigh-dose IV
corticosteroids (e.g.,methylprednisolone 2–4
mg/kg/day
or equivalent)-
Once sym
ptoms
have resolved to baseline orG
rade 1, convertto equivalent oralcorticosteroid dose and then taperslow
lyover at least 1 m
onth-
Anticipate the use ofem
piric antibiotics untilinfection is excluded
-A
nticipate the use ofadditionalim
munosuppressive agents
if symptom
s donot im
prove in 48–72 hours(e.g.,inflixim
ab,m
ycophenolate, cyclophosphamide)
-A
ssesspatient &
family understanding of
toxicity and rationale for treatment
discontinuation-
Identify barriers to adherence,specificallycom
pliance with m
edication, physical activity
Grade 1 (M
ild)A
symptom
atic;clinical or diagnostic observations only; intervention not indicated
Grade 2 (M
oderate)S
ymptom
atic; medical intervention
indicated; limiting instrum
ental A
DLs
Grade 3 (Severe)
Severe sym
ptoms; lim
iting self-care A
DLs; oxygen indicated
Grade 4 (Potentially Life-Threatening)
Life-threatening respiratory comprom
ise; urgent intervention indicated (tracheostom
y, intubation)
Grade 5
(Death)
Grade 1 (M
ild)G
rade 2 (Moderate)
Decreased
oxygen saturation with
exercise (e.g.,pulse ox <88%);
intermittent supplem
ental oxygen
Grade 3 (Severe)
Decreased
oxygen saturation at rest (e.g.,pulse ox <88%
)
Grade 4 (Potentially Life-Threatening)
Life-threatening airway com
promise; urgent
intervention indicated (tracheostomy,
intubation)
Grade 5
(Death)
Prevention-
No know
n interventions
Nursing Im
plementation:
-Identify high-risk
individuals(e.g.,asthm
a, CO
PD)and those w
ith cardiopulmonary sym
ptoms prior to initiating im
munotherapy. Establish a thorough baseline
-Educate patients thatnew
pulmonary sym
ptoms
should be reported imm
ediately-
Anticipate thatthe steroid requirements to m
anage pneumonitis are high (1 –4
mg/kg/day)and patientw
ill be on corticosteroid therapy for at least 1m
onth-
Educate patients and family
about the rationale for discontinuation of imm
unotherapy inpatients w
hodo develop
moderate or severe pneum
onitis
RED FLAGS:
-Risk of acute onset
-Risk of m
ortality ifpneumonitistreatm
ent isdelayed-
Risk of pneumonitis is greater in patientsreceiving
combination im
munotherapy
regimens
Copyright ©
2017 Melanom
a Nursing Initiative.
AD
L = activities of daily living;CO
PD
= chronic obstructive pulmonary disease
© 2017 The M
elanoma N
ursing Initiative. All rights reserved
ww
w.them
elanomanurse.org
Pneumonitis Page 2 of 2
Care Step Pathw
ay–
Pneumonitis
(inflamm
ation oflung alveoli)
Nursing Assessm
ent
Look:-
Does the patient appear uncom
fortable?-
Did the patienthave difficulty w
alking to the examroom
?O
r going up stairs?-
Does the patient appear shortof breath?
-Is the patient tachypneic?
-D
oes the patient appear to be in respiratory distress?
Grading Toxicity
Pneumonitis
Definition: A
disorder characterized byinflam
mation focally
or diffuselyaffecting the lung parenchym
a
HypoxiaD
efinition: Adisorder characterized by decrease in the level of oxygen to the body
Listen:-
Has the patient noted any change in breathing?
-D
oes the patient feelshort of breath?-
Does the patient note new
dyspnea on exertion?-
Does the patient notice a new
cough? Or a change in an
existing cough?-
Have sym
ptoms w
orsened? -
Are sym
ptoms lim
itingA
DLs?
-A
ssociated symptom
s? o
Fatigue o
Wheezing
Recognize:
-Is the pulse oxim
etry low? Is itlow
er than baselineor
compared
with
last visit?Is it low
on exertion?-
Is there a pre-existing pulmonary autoim
mune condition
(i.e.,sarcoidosis)?-
Is there a history ofprior respiratory comprom
ise(e.g.,
asthma, C
OP
D,congestive heart failure)?
-H
as the patient experienced other imm
une-related adverse effects?
Managem
ent
Overall Strategy:
-Assess for other etiologies such as infection, pulm
onary embolism
, progressive lung metastases,or lung disease
-Early intervention to m
aintain or improve physical function and im
pact on QO
L-
Assess pulse oximetry (resting & on exertion) at baseline and at each visit to assist in identifying a decrease at early onset.
Grade 1 (M
ild)-
Anticipate im
munotherapy to continue
-C
ontinue to monitor via radiology
testing(q 2–4
weeks, as needed)
-R
eview sym
ptoms to w
atch for with
patient and family,and rem
ember t o
assess at every subsequent visit
Grade 2 (M
oderate)-
Imm
unotherapyto be w
ithheldfor G
rade 2events (resum
e when G
rade 0/1)-
Imm
unotherapy to be discontinued forrecurrent (pem
brolizumab, nivolum
ab) orpersistent G
rade 2 events (ipilimum
ab,pem
brolizumab, nivolum
ab)-
Anticipate treatm
ent with:
oC
orticosteroids (e.g.,prednisone 1–2m
g/kg/dayor equivalent)until
sy mptom
sim
prove to baseline,andthen slow
taper over at least 1m
ontho
If symptom
s do not improve w
ithin 48–72 hours, corticosteroid
dose will be
escalated. IV corticosteroids may be
consideredo
Additional supportive care m
edicationsm
ay also be initiated-
Anticipatory guidance on proper
administrati on
-A
nticipate the use of empiric antibiotics until
infection is excluded-
Anticipate that bronchoscopy m
ay beordered by provider
-A
ssess patient & fam
ily understanding ofrecom
mendations and rationale
-Identify barriers to adherence
Grades 3–4 (Severe or Life-Threatening)
-D
iscontinue imm
unotherapy for Grade 3/4
events-
Patient w
ill likely need to be admitted to the
hos pital for furthermanagem
ent andsupportive care
-A
nticipate the use of high-dose IVcorticosteroids (e.g.,m
ethylprednisolone 2–4m
g/kg/dayor equivalent)
-O
nce symptom
s have resolved to baseline orG
rade 1, convert to equivalent oralcorticosteroid dose and then taper slow
lyover at least 1 m
onth-
Anticipate the use of em
piric antibiotics untilinfection is excluded
-A
nticipate the use of additionalim
munosuppressive agents if sym
ptoms do
not improve in 48–72 hours
(e.g.,infliximab,
mycophenolate, cyclophospham
ide)-
Assess patient &
family understanding of
toxicity and rationale for treatment
discontinuation-
Identify barriers to adherence, specificallycom
pliance with m
edication, physical activity
Grade 1 (M
ild)A
symptom
atic;clinical ordiagnostic observations only;intervention not indicated
Grade 2 (M
oderate)S
ymptom
atic; medical intervention
indicated; limiting instrum
ental A
DLs
Grade 3 (Severe)
Severe sym
ptoms; lim
iting self-care A
DLs; oxygen indicated
Grade 4 (Potentially Life-Threatening)
Life-threatening respiratory comprom
ise;urgentintervention indicated (tracheostom
y,intubation)
Grade 5
(Death)
Grade 1 (M
ild)G
rade 2 (Moderate)
Decreased
oxygen saturation with
exercise (e.g.,pulse ox <88%);
intermittent supplem
entaloxygen
Grade 3 (Severe)
Decreased
oxygen saturation atrest (e.g.,pulse ox <88%
)
Grade 4 (Potentially Life-Threatening)
Life-threatening airway com
promise;urgent
intervention indicated (tracheostomy,
intubation)
Grade 5
(Death)
Prevention-
No know
n interventions
Nursing Im
plementation:
-Identify high-risk
individuals(e.g., asthm
a, CO
PD)and those w
ith cardiopulmonary sym
ptoms prior to initiating im
munotherapy. Establish a thorough baseline
-Educate patients that new
pulmonary sym
ptoms should be reported im
mediately
-Anticipate that the steroid requirem
ents to manage pneum
onitis are high (1 –4m
g/kg/day) and patient will be on corticosteroid therapy for at least 1
month
-Educate patients and fam
ily about the rationale for discontinuation of imm
unotherapy in patients who do develop
moderate or severe pneum
onitis
RED FLAGS:
-Risk of acute onset
-Risk of m
ortality if pneumonitis treatm
ent is delayed-
Risk of pneumonitis is greater in patients receiving com
bination imm
unotherapy regimens
Copyright ©
2017 Melanom
a Nursing Initiative.
AD
L = activities of daily living; CO
PD
= chronic obstructive pulmonary disease
© 2017 The M
elanoma N
ursing Initiative. All rights reserved
ww
w.them
elanomanurse.org
Arthralgias and A
rthritis Page 1 of 3
Care Step Pathw
ay-Arthralgias and Arthritis
Nursing Assessm
entLook:-
Does the patient appear uncom
fortable?-
Does the patient appear unw
ell?-
Is their gait affected?-
Obvious sw
ollen, or deformed joint(s)?
-Is the patient having trouble getting up and dow
nstairs?
Grading Toxicity
Arthralgia
Definition: A
disorder characterized by a sensation of marked discom
fort in a joint
Arthritis
Definition: A disorder characterized by inflam
mation involving a joint
Listen:-
Have sym
ptoms w
orsened?-
Are sym
ptoms lim
iting AD
Ls?-
Are sym
ptoms increasing the patient’s risk for
fall? Other safety issues?
-A
ssociated symptom
s?o
Fatigue (new or w
orsening)
Recognize:
-Is there a pre-existing autoim
mune dysfunction?
-Is there a history of prior orthopedic injury, D
JD, O
A, R
A?
-O
ther imm
une-related adverse effects-
Three subtypes of inflamm
atory arthritis associated with
checkpoint inhibitors:1.P
olyarthritis similar to rheum
atoid arthritis2.True reactive arthritis w
ith conjunctivitis, urethritis, andol igoarthritis
3.Subtype sim
ilar to seronegative spondyloarthritisw
ithinflam
matory back pain and predom
inantly larger jointinvolvem
ent.
Managem
ent
Overall Strategy:
-Assess for other etiologies,such as lytic
or osseous metastasis
-Early
intervention to maintain orim
prove physical function and impact on Q
OL; sym
ptomcontrol through the treatm
ent of inflamm
ation and pain is often achieved w
ith NS
AIDs, corticosteroids, and otheradjunct therapies
Grade 1 (M
ild) -
Anticipate im
munotherapy to continue
-E
ncourage physical activityo
30 minutes
of low-to-m
oderate–intensity
physical activity 5 days perw
eek can improve physical
conditioning, sleep, and decreasespain perception
oFor physically inactive patients,advise supervised exercise,resistance training
oO
ther:yoga, tai chi,Qigong, Pilates,
aquaticexercise, focused dance
program-
Anticipate use of analgesiao
Low-dose N
SA
IDs
Topical:diclofenac (gel orpatch).B
est for localized,lim
ited,superficial jointinflam
mation or foruse in
patients who
cannot tolerate oralN
SA
IDs
O
ral:ibuprofen, naproxen,celecoxib
Anticipatory guidance on
proper administration
-A
ssess patientandfam
ily understanding of recom
mendations and rationale
oIdentify barriers to adherence
If symptom
s do notimprove in 4–6
weeks, escalate to nextlevel of therapy
Grade 2 (M
oderate)-
Ipilimum
ab to be withheld forany G
rade 2 event (until G
rade 0/1) and discontinued forevents persisting ≥6 w
eeks orinability toreduce steroid dose to 7.5 m
g prednisone orequivalent per day
-D
ose of pembrolizum
ab or nivolumab to be
held as to not make sym
ptoms w
orse-
Pem
brolizumab or nivolum
ab to be discontinued for G
rade 2 events persisting ≥12 w
eeks-
Continue to encourage physical activity
-A
nticipate use of analgesiao
NS
AID
s
Oral:ibuprofen, naproxen, celecoxib
Anticipatory guidance on proper
administration
-A
nticipate referralto rheumatology for
collaborative managem
ent and consideration of adjuncttreatm
ent-
Anticipate pre-visit assessm
ent: CB
C, E
SR
, C
RP
, BU
N/C
R&
aminotransferases, A
NA
, RF
oIntraarticularsteroids to be used forsignificant sym
ptomatic joint(s)
oLow
-dose corticosteroids (0.5 –1
mg/kg/day) to be used
Anticipatory guidance on proper
administration
D
urationof corticosteroid therapy
isusually lim
ited,lasting forabout 4–6w
eeks, with possible resolution of
symptom
sw
ithin weeks to m
onths oftreatm
ent-
Assess
patient &fam
ily understanding oftoxicity, rationale for treatm
ent hold (ifapplicable)o
Identify barriers to adherence
If symptom
s do notimprove in 4–6 w
eeks,escalate to
nextlevel of therapy
Grades 3-4 (Severe or Life-Threatening)
-P
embrolizum
ab or nivolumab to be w
ithheld for first-occurrence G
rade 3/4 eventanddiscontinued if:
oG
rade 3/4 event recurso
Persists ≥12 w
eeks-
Ipilimum
ab to be discontinued for any Grade 3/4 event.
-H
igh-dose steroidsto be used (1-1.5 m
g/kg) daily; [rapid effect w
ithin days]o
Anticipatory guidance on proper adm
inistration o
Onset of action is
rapid, typically within days
-A
nticipate referralto rheumatology forcollaborative
managem
ent and consideration ofadjunct treatment
oN
on-biologicagents (m
ore likely to be recomm
ended)
Conventional synthetic
DM
AR
Ds
(csDM
AR
Ds),
which have a delayed effectand take w
eeks to w
ork:
Methotrexate
S
ulfasalazine*
Hydroxychloroquine
Leflunom
ideo
Biologic agents
(less likelyto be recom
mended)
B
iologic DM
AR
Ds (bD
MA
RD
s)
TNF inhibitors
Infliximab
E
tanercept
Adalim
umab
G
olimum
ab
Certolizum
ab pegol
Anti B
-cellagents (CD
-20 blocking)
Rituxim
ab o
Agents N
OT advised
Interleukin (IL)-6 receptor blocking agent(tocilizum
ab) and JAK
inhibitors (tofacitinib) due to risk of colonic
perforation
T cell co-stimulation inhibitor (abatacept) as it
directly opposes the mechanism
ofcheckpointblockade agents
oA
ssesspatient &
family understanding of toxicity and
rationale fortreatmentdiscontinuation
oIdentify barriers to adherence,specifically com
pliance w
ith medication,physical activity
*Sulfasalazine is associated w
ith rash; do not use in patientsw
ith history of orcurrent treatment-related derm
atitis
Grade 1 (M
ild)M
ild painG
rade 2 (Moderate)
Moderate pain; lim
iting instrum
ental AD
L
Grade 3 (Severe)
Severe pain; lim
iting self-care AD
LG
rade 4 (Potentially Life-Threatening)G
rade 5 (Death)
Grade 1 (M
ild)M
ild pain with inflam
mation,
erythema, or joint sw
elling
Grade 2 (M
oderate)M
oderate pain associated with
signs of inflamm
ation, erythema,
or joint swelling; lim
iting instrum
ental AD
L
Grade 3 (Severe)
Severe pain associated w
ith signs of inflam
mation, erythem
a, or joint sw
elling; irreversible joint damage;
disabling; limiting self-care A
DL
Grade 4 (Potentially Life-Threatening)
Grade 5 (D
eath)
Prevention-
No know
n interventions
Nursing Im
plementation:
-Identify high-risk individuals and
those with underlying autoim
mune dysfunction
-E
ducate patientsthatarthralgias and arthritis
are the mostcom
monly reported rheum
atic and musculoskeletalirA
Es w
ith checkpoint inhibitors-
Arthritis-like sym
ptoms can range from
mild (m
anaged wellw
ith NS
AID
s and low dose corticosteroids)to severe and erosive (requiring m
ultiple imm
unosuppressant medications)
-A
nticipate that the steroid requirements to m
anage arthralgias can be much higher (i.e.,up to 1.5 m
g/kg/day) thantypically required to m
anage "classic"inflamm
atory arthritis-
Educate patients
that symptom
s can persistbeyond treatment com
pletion or discontinuation
RED FLAGS:
-Risk of fall due to m
obilityissue
AD
Ls = activities ofdailyliving; A
NA
= antinuclear antibody;BU
N = blood urea nitrogen; C
BC
= complete blood count; C
R = creatinine; C
RP
= C-reactive protein; D
JD = degenerative joint disease;
DM
AR
D= disease-m
odifying antirheumatic
drug; ES
R =
erythrocyte sedimentation rate; N
SA
ID= nonsteroidal anti-inflam
matory drug; O
A = osteoarthritis; Q
OL = quality of life;R
A =
rheumatoid
arthritis; RF = rheum
atoid factor;TNF = tum
or necrosis factor
Copyright ©
2017 Melanom
a Nursing Initiative.
© 2017 The M
elanoma N
ursing Initiative. All rights reserved
ww
w.them
elanomanurse.org
Arthralgias and A
rthritis Page 2 of 3
Care Step Pathw
ay-Arthralgias and
Arthritis
Nursing Assessm
entLook:-
Does the patient appear uncom
fortable?-
Does the patient appear unw
ell?-
Is their gait affected?-
Obvious sw
ollen,ordeformed joint(s)?
-Is the patienthaving trouble getting up and dow
n stairs?
Grading Toxicity
Arthralgia
Definition: A
disorder characterized bya sensation ofm
arked discomfort in a joint
Arthritis
Definition: A
disorder characterized byinflam
mation involving a joint
Listen:-
Have sym
ptoms w
orsened? -
Are sym
ptoms lim
iting AD
Ls?-
Are sym
ptoms increasing the patient’s risk for
fall? Othersafety issues?
-A
ssociated symptom
s?o
Fatigue (new or w
orsening)
Recognize:
-Is there a pre-existing autoim
mune dysfunction?
-Is there a history ofpriororthopedic injury, D
JD, O
A, R
A?
-O
ther imm
une-related adverse effects-
Three subtypes ofinflamm
atory arthritis associated with
checkpointinhibitors:1.P
olyarthritissim
ilar to rheumatoid arthritis
2.True reactive arthritis with conjunctivitis, urethritis,and
oligoarthritis3.S
ubtype similar to seronegative spondyloarthritis
with
inflamm
atory back pain and predominantly larger joint
involvement.
Managem
ent
Overall Strategy:
-Assess for other etiologies,such as lytic or osseous m
etastasis-
Early intervention to maintain or im
prove physical function and impact on Q
OL; sym
ptomcontrol through the treatm
ent of inflamm
ation and pain is often achievedw
ith NS
AIDs, corticosteroids, and other adjunct therapies
Grade 1 (M
ild) -
Anticipate im
munotherapy to continue
-E
ncourage physical activityo
30 minutes of low
-to-moderate–
intensity physical activity 5 days perw
eek can improve physical
conditioning, sleep, and decreasespain perception
oFor physically inactive patients,advise supervised exercise,resistance traini ng
oO
ther: yoga, tai chi, Qigong, Pilates,
aquatic exercise, focused danceprogram
-A
nticipate use of analgesiao
Low-dose N
SA
IDs
Topical:diclofenac (gel orpatch).B
est for localized,lim
ited,superficial jointinflam
mation or for use i n
patients who
cannot tolerate oralN
SA
IDs
O
ral:ibuprofen, naproxen,celecoxib
Anticipatory guidance o n
proper administration
-A
ssess patient andfam
ily understandingof recom
mendations and rationale
oIdentify barriers to adherence
If symptom
s do not improve in 4–6
weeks, escalate to next level of therapy
Grade 2 (M
oderate)-
Ipilimum
ab to be withheld for any G
rade 2event (until G
rade 0/1) and discontinued forevents persisting ≥6 w
eeks or inability toreduce steroid dose to 7.5 m
g prednisone orequivalent per day
-D
ose of pembrolizum
ab or nivolumab t o be
held as to not make sym
ptoms w
orse-
Pem
brolizumab or nivolum
ab to bediscontinued for G
rade 2 events persisting ≥1 2w
eeks-
Continue to encourage physical activity
-A
nticipate use of analgesiao
NS
AID
s
Oral:ibuprofen, naproxen, celecoxib
Anticipatory guidance on proper
administration
-A
nticipate referral to rheumatology for
collaborative managem
ent and considerati onof adjunct treatm
ent-
Anticipate pre-visit assessm
ent: CB
C, E
SR
,C
RP
, BU
N/C
R&
aminotransferases, A
NA
, RF
oIntraarticular steroids to be used forsignificant sym
ptomatic joint(s)
oLow
-dose corticosteroids (0.5 –1
mg/kg/day) to be used
Anticipatory guidance on proper
administration
D
uration of corticosteroid therapy isusually lim
ited, lasting for about 4–6w
eeks, with possible resolution of
symptom
s within w
eeks to months of
treatment
-A
ssess patient & fam
ily understanding oftoxicity, rationale for treatm
ent hold (ifapplicable)o
Identify barriers to adherence
If symptom
s do not improve in 4–6 w
eeks, escalate to next level of therapy
Grades 3-4 (Severe or Life-Threatening)
-P
embrolizum
ab or nivolumab to be w
ithheld for first-occurrence G
rade 3/4 event anddiscontinued if:
oG
rade 3/4 event recurso
Persists ≥12 w
eeks-
Ipilimum
ab to be discontinued for any Grade 3/4 event.
-H
igh-dose steroids to be used (1-1.5 mg/kg) daily; [rapi d
effect within days]
oA
nticipatory guidance on proper administration
oO
nset of action is rapid, typically within days
-A
nticipate referral to rheumatology for collaborative
managem
ent and consideration of adjunct treatment
oN
on-biologic agents (more likely to be recom
mended)
C
onventional synthetic DM
AR
Ds
(csDM
AR
Ds),
which have a delayed effect and take w
eeks tow
o rk:
Methotrexate
S
ulfasalazine*
Hydroxychloroquine
Lef lunom
ideo
Biologic agents (less likely to be recom
mended)
B
iologic DM
AR
Ds (bD
MA
RD
s)
TNF inhibitors
Infliximab
E
tanercept
Adalim
umab
G
olimum
a b
Certolizum
ab pegol
Anti B
-cell agents (CD
-20 blocking)
Rituxim
abo
Agents N
OT advis ed
Interleukin (IL)-6 receptor blocking agent(tocilizum
ab) and JAK
inhibitors (tofacitinib) d ueto risk of colonic perforation
T cell co-stim
ulation inhibitor (abatacept) as itdirectly opposes the m
echanism of checkpoint
blockade agentso
Assess patient &
family understanding of toxicity and
r ationale for treatment discontinuation
oIdentify barriers to adherence, specifically com
pliancew
ith medication, physical activity
*Sulfasalazine is associated w
ith rash; do not use in patientsw
ith history of or current treatment-related derm
atitis
Grade 1 (M
ild)M
ild painG
rade 2 (Moderate)
Moderate pain; lim
itinginstrum
ental AD
L
Grade 3 (Severe)
Severe pain; lim
iting self-care AD
LG
rade 4 (Potentially Life-Threatening)G
rade 5 (Death)
Grade 1 (M
ild)M
ild pain with inflam
mation,
erythema, or jointsw
elling
Grade 2 (M
oderate)M
oderate pain associated with
signs of inflamm
ation, erythema,
or jointswelling; lim
iting instrum
ental AD
L
Grade 3 (Severe)
Severe pain associated w
ith signsof inflam
mation, erythem
a,or jointsw
elling; irreversible jointdamage;
disabling; limiting self-care A
DL
Grade 4 (Potentially Life-Threatening)
Grade 5 (D
eath)
Prevention -
No know
n interventions
Nursing Im
plementation:
-Identify high-risk individuals and
those with underlying autoim
mune dysfunction
-E
ducate patientsthatarthralgias and arthritis
are the mostcom
monly reported rheum
atic and musculoskeletalirA
Es w
ith checkpoint inhibitors-
Arthritis-like sym
ptoms can range from
mild (m
anaged wellw
ith NS
AID
s and low dose corticosteroids)to severe and erosive (requiring m
ultiple imm
unosuppressant medications)
-A
nticipate that the steroid requirements to m
anage arthralgias can be much higher (i.e.,up to 1.5 m
g/kg/day) thantypically required to m
anage "classic"inflamm
atory arthritis-
Educate patients
that symptom
s can persistbeyond treatment com
pletion or discontinuation
RED FLAGS:
-Risk of fall due to m
obilityissue
AD
Ls = activities ofdailyliving; A
NA
= antinuclear antibody;BU
N = blood urea nitrogen; C
BC
= complete blood count; C
R = creatinine; C
RP
= C-reactive protein; D
JD = degenerative joint disease;
DM
AR
D= disease-m
odifying antirheumatic
drug; ES
R =
erythrocyte sedimentation rate; N
SA
ID= nonsteroidal anti-inflam
matory drug; O
A = osteoarthritis; Q
OL = quality of life;R
A =
rheumatoid
arthritis; RF = rheum
atoid factor;TNF = tum
or necrosis factor
Copyright ©
2017 Melanom
a Nursing Initiative.
© 2017 The M
elanoma N
ursing Initiative. All rights reserved
ww
w.them
elanomanurse.org
Arthralgias and A
rthritis Page 3 of 3
Care Step Pathw
ay-Arthralgias and
Arthritis
Nursing Assessm
entLook:-
Does the patient appear uncom
fortable?-
Does the patient appear unw
ell?-
Is their gait affected?-
Obvious sw
ollen,ordeformed joint(s)?
-Is the patienthaving trouble getting up and dow
n stairs?
Grading Toxicity
Arthralgia
Definition: A
disorder characterized bya sensation ofm
arked discomfort in a joint
Arthritis
Definition: A
disorder characterized byinflam
mation involving a joint
Listen:-
Have sym
ptoms w
orsened? -
Are sym
ptoms lim
iting AD
Ls?-
Are sym
ptoms increasing the patient’s risk for
fall? Othersafety issues?
-A
ssociated symptom
s?o
Fatigue (new or w
orsening)
Recognize:
-Is there a pre-existing autoim
mune dysfunction?
-Is there a history ofpriororthopedic injury, D
JD, O
A, R
A?
-O
ther imm
une-related adverse effects-
Three subtypes ofinflamm
atory arthritis associated with
checkpointinhibitors:1.P
olyarthritissim
ilar to rheumatoid arthritis
2.True reactive arthritis with conjunctivitis, urethritis,and
oligoarthritis3.S
ubtype similar to seronegative spondyloarthritis
with
inflamm
atory back pain and predominantly larger joint
involvement.
Managem
ent
Overall Strategy:
-Assess for other etiologies,such as lytic
or osseous metastasis
-Early
intervention to maintain orim
prove physical function and impact on Q
OL; sym
ptomcontrol through the treatm
ent of inflamm
ation and pain is often achieved w
ith NS
AIDs, corticosteroids, and otheradjunct therapies
Grade 1 (M
ild) -
Anticipate im
munotherapy to continue
-E
ncourage physical activityo
30 minutes
of low-to-m
oderate–intensity
physical activity 5 days perw
eek can improve physical
conditioning, sleep, and decreasespain perception
oFor physically inactive patients,advise supervised exercise,resistance training
oO
ther:yoga, tai chi,Qigong, Pilates,
aquaticexercise, focused dance
program-
Anticipate use of analgesiao
Low-dose N
SA
IDs
Topical:diclofenac (gel orpatch).B
est for localized,lim
ited,superficial jointinflam
mation or foruse in
patients who
cannot tolerate oralN
SA
IDs
O
ral:ibuprofen, naproxen,celecoxib
Anticipatory guidance on
proper administration
-A
ssess patientandfam
ily understanding of recom
mendations and rationale
oIdentify barriers to adherence
If symptom
s do notimprove in 4–6
weeks, escalate to nextlevel of therapy
Grade 2 (M
oderate)-
Ipilimum
ab to be withheld forany G
rade 2 event (until G
rade 0/1) and discontinued forevents persisting ≥6 w
eeks orinability toreduce steroid dose to 7.5 m
g prednisone orequivalent per day
-D
ose of pembrolizum
ab or nivolumab to be
held as to not make sym
ptoms w
orse-
Pem
brolizumab or nivolum
ab to be discontinued for G
rade 2 events persisting ≥12 w
eeks-
Continue to encourage physical activity
-A
nticipate use of analgesiao
NS
AID
s
Oral:ibuprofen, naproxen, celecoxib
Anticipatory guidance on proper
administration
-A
nticipate referralto rheumatology for
collaborative managem
ent and consideration of adjuncttreatm
ent-
Anticipate pre-visit assessm
ent: CB
C, E
SR
, C
RP
, BU
N/C
R&
aminotransferases, A
NA
, RF
oIntraarticularsteroids to be used forsignificant sym
ptomatic joint(s)
oLow
-dose corticosteroids (0.5 –1
mg/kg/day) to be used
Anticipatory guidance on proper
administration
D
urationof corticosteroid therapy
isusually lim
ited,lasting forabout 4–6w
eeks, with possible resolution of
symptom
sw
ithin weeks to m
onths oftreatm
ent-
Assess
patient &fam
ily understanding oftoxicity, rationale for treatm
ent hold (ifapplicable)o
Identify barriers to adherence
If symptom
s do notimprove in 4–6 w
eeks,escalate to
nextlevel of therapy
Grades 3-4 (Severe or Life-Threatening)
-P
embrolizum
ab or nivolumab to be w
ithheld for first-occurrence G
rade 3/4 eventanddiscontinued if:
oG
rade 3/4 event recurso
Persists ≥12 w
eeks-
Ipilimum
ab to be discontinued for any Grade 3/4 event.
-H
igh-dose steroidsto be used (1-1.5 m
g/kg) daily; [rapid effect w
ithin days]o
Anticipatory guidance on proper adm
inistration o
Onset of action is
rapid, typically within days
-A
nticipate referralto rheumatology forcollaborative
managem
ent and consideration ofadjunct treatment
oN
on-biologicagents (m
ore likely to be recomm
ended)
Conventional synthetic
DM
AR
Ds
(csDM
AR
Ds),
which have a delayed effectand take w
eeks to w
ork:
Methotrexate
S
ulfasalazine*
Hydroxychloroquine
Leflunom
ideo
Biologic agents
(less likelyto be recom
mended)
B
iologic DM
AR
Ds (bD
MA
RD
s)
TNF inhibitors
Infliximab
E
tanercept
Adalim
umab
G
olimum
ab
Certolizum
ab pegol
Anti B
-cellagents (CD
-20 blocking)
Rituxim
ab o
Agents N
OT advised
Interleukin (IL)-6 receptor blocking agent(tocilizum
ab) and JAK
inhibitors (tofacitinib) due to risk of colonic
perforation
T cell co-stimulation inhibitor (abatacept) as it
directly opposes the mechanism
ofcheckpointblockade agents
oA
ssesspatient &
family understanding of toxicity and
rationale fortreatmentdiscontinuation
oIdentify barriers to adherence,specifically com
pliance w
ith medication,physical activity
*Sulfasalazine is associated w
ith rash; do not use in patientsw
ith history of orcurrent treatment-related derm
atitis
Grade 1 (M
ild)M
ild painG
rade 2 (Moderate)
Moderate pain; lim
itinginstrum
ental AD
L
Grade 3 (Severe)
Severe pain; lim
iting self-care AD
LG
rade 4 (Potentially Life-Threatening)G
rade 5 (Death)
Grade 1 (M
ild)M
ild pain with inflam
mation,
erythema, or jointsw
elling
Grade 2 (M
oderate)M
oderate pain associated with
signs of inflamm
ation, erythema,
or jointswelling; lim
iting instrum
ental AD
L
Grade 3 (Severe)
Severe pain associated w
ith signsof inflam
mation, erythem
a,or jointsw
elling; irreversible jointdamage;
disabling; limiting self-care A
DL
Grade 4 (Potentially Life-Threatening)
Grade 5 (D
eath)
Prevention-
No know
n interventions
Nursing Im
plementation:
-Identify high-risk individuals and those w
ith underlying autoimm
une dysfunction-
Educate patients that arthralgias and arthritis are the m
ost comm
only reported rheumatic and m
usculoskeletal irAE
s with checkpoint inhibitors
-A
rthritis-like symptom
s can range from m
ild (managed w
ell with N
SA
IDs and low
dose corticosteroids)to severe and erosive (requiring multiple im
munosuppressant m
edications)-
Anticipate that the steroid requirem
ents to manage arthralgias can be m
uch higher (i.e., up to 1.5 mg/kg/day) than
typically required to manage "classic"inflam
matory arthritis
-E
ducate patients that symptom
s can persist beyond treatment com
pletion or discontinuation
RED FLAGS:
-Risk of fall due to m
obility issue
AD
Ls = activities of daily living; AN
A= antinuclear antibody; B
UN
= blood urea nitrogen; CB
C = com
plete blood count; CR
= creatinine; CR
P = C
-reactive protein; DJD
= degenerative joint disease; D
MA
RD
= disease-modifying antirheum
atic drug; ES
R = erythrocyte sedim
entation rate; NS
AID
= nonsteroidal anti-inflamm
atory drug; OA
= osteoarthritis; QO
L = quality of life;RA
= rheumatoid
arthritis; RF = rheum
atoid factor;TNF = tum
or necrosis factor
Copyright ©
2017 Melanom
a Nursing Initiative.
Care Step Pathw
ay –N
europathy (motor or sensory nerve im
pairment or dam
age)
Nursing Assessm
ent
Look:-
Does the patient appear w
eak?-
Does the patient appear uncom
fortable?-
Altered am
bulation or general movem
ent?-
If muscular w
eakness is present, any respiratory difficulties apparent?
Grading of N
europathy:
Listen:-
Does the patient report w
eakness (unilateral or bilateral)?
-D
oes the patient report new or w
orsened pain, num
bness, or tingling?-
Does the patient report difficulty w
alking or holding item
s?
Recognize:
-M
otor deficits-
Sensory deficits
-M
ental status changes-
Paresthesias
-Laboratory values
-D
oes the patient have diabetes mellitus?
-A
re there neurologic signs and symptom
s?-
Results of prior im
aging o
Metastases to spinal cord
oO
ther metastases that m
ay cause symptom
s
Managem
entO
verall Strategy:-
Rule out infectious, non-infectious, disease-related etiologies
-H
igh-dose steroids (1–2 mg/kg/day prednisone or equivalent) to be used
-Ipilim
umab to be w
ithheld for Grade 2 event, nivolum
ab for firstoccurrence of Grade 3 event, and pem
brolizumab based on disease severity; ipilim
umab to be discontinued for G
rade 2 events persisting ≥6 w
eeks or inability to reduce steroid dose to ≤7.5 mg prednisone or equivalent per day; pem
brolizumab or nivolum
ab to be discontinued for Grade 3/4 events that recur,
persist ≥12 weeks, or inability to reduce steroid dose to ≤10 m
g prednisone or equivalent per day -
Neurology consulto
Consideration of electrom
yelogram and nerve conduction tests
oIm
mune globulin infusions
oP
lasmapheresis
-Taper steroids slow
ly over at least 4 weeks once sym
ptoms im
prove-
If needed, obtain physical therapy or occupational therapy consult (for both functional assessment and evaluate safety of patient at hom
e)-
Supportive m
edications for symptom
atic managem
ent
Grade 1 (M
ild)P
eripheral Motor:
-A
symptom
atic; clinical or diagnostic observations only
-N
o intervention indicated
Peripheral Sensory:
Asym
ptomatic;loss of deep tendon
reflexes or paresthesia
Grade 2 (M
oderate)P
eripheral Motor:
Moderate sym
ptoms; lim
iting A
DLs
Peripheral Sensory:
Moderate sym
ptoms; lim
iting A
DLs
Grade 3 (Severe)
Peripheral M
otor:S
evere symptom
s; limiting self-
care AD
Ls; requires assistive devices
Peripheral Sensory:
Severe sym
ptoms; lim
iting self-care A
DLs
Grade 4 (Potentially Life-Threatening)
Peripheral M
otor:Life-threatening;urgent intervention indicated
Peripheral Sensory:
Life-threatening;urgent intervention indicated
Grade 5 (D
eath)
Nursing Im
plementation:
-C
ompare baseline assessm
ent;grade & docum
ent neuropathy and etiology (diabetic, medication, vascular, chem
otherapy)-
Early identification and evaluation of patient sym
ptoms
-E
arly intervention with lab w
ork and office visit if neuropathy symptom
ssuspected
RED FLAGS:
-G
uillain–Barré syndrome
-M
yasthenia gravis
*Steroid
taperinstructions/calendarasa
guidebutnotan
absolute-
Tapershouldconsiderpatient’s
currentsymptom
profile-
Close
follow-up
inperson
orbyphone,based
onindividualneed
&sym
ptomatology
-A
nti-acidtherapy
dailyas
gastriculcerprevention
while
onsteroids
-R
eviewsteroid
medication
sideeffects:m
oodchanges
(anger,reactive,hyperaware,euphoric,m
ania), increasedappetite,interrupted
sleep,oralthrush,fluidretention
-B
ealertto
recurringsym
ptoms
assteroids
taperdown
& reportthem
(tapermay
needto
beadjusted)
Long-term
high-dosesteroids:
-C
onsiderantimicrobialprophylaxis
(sulfamethoxazole/trim
ethoprim double dose M
/W/F; single dose if used
daily) or alternative if sulfa-allergic (e.g., atovaquone [Mepron
®]1500 mg po daily)
-C
onsideradditionalantiviraland antifungalcoverage-
Avoid
alcohol/acetaminophen
orotherhepatoxins
AD
Ls = activities of daily living
Copyright ©
2017 Melanom
a Nursing Initiative.
© 2017 The M
elanoma N
ursing Initiative. All rights reserved
ww
w.them
elanomanurse.org
Neuropathy Page 1 of 2
Care Step Pathw
ay –N
europathy (motor or sensory nerve im
pairment or dam
age)
Nursing Assessm
ent
Look:-
Does the patient appear w
eak?-
Does the patient appear uncom
fortable?-
Altered am
bulation or general movem
ent?-
If muscular w
eakness is present, any respiratory difficulties apparent?
Grading of N
europathy:
Listen:-
Does the patient report w
eakness (unilateral or bilateral)?
-D
oes the patient report new or w
orsened pain, num
bness, or tingling?-
Does the patient report difficulty w
alking or holding item
s?
Recognize:
-M
otor deficits-
Sensory deficits
-M
ental status changes-
Paresthesias
-Laboratory values
-D
oes the patient have diabetes mellitus?
-A
re there neurologic signs and symptom
s?-
Results of prior im
aging o
Metastases to spinal cord
oO
ther metastases that m
ay cause symptom
s
Managem
entO
verall Strategy:-
Rule out infectious, non-infectious, disease-related etiologies
-H
igh-dose steroids (1–2 mg/kg/day prednisone or equivalent) to be used
-Ipilim
umab to be w
ithheld for Grade 2 event, nivolum
ab for firstoccurrence of Grade 3 event, and pem
brolizumab based on disease severity; ipilim
umab to be discontinued for G
rade 2 events persisting ≥6 w
eeks or inability to reduce steroid dose to ≤7.5 mg prednisone or equivalent per day; pem
brolizumab or nivolum
ab to be discontinued for Grade 3/4 events that recur,
persist ≥12 weeks, or inability to reduce steroid dose to ≤10 m
g prednisone or equivalent per day -
Neurology consulto
Consideration of electrom
yelogram and nerve conduction tests
oIm
mune globulin infusions
oP
lasmapheresis
-Taper steroids slow
ly over at least 4 weeks once sym
ptoms im
prove-
If needed, obtain physical therapy or occupational therapy consult (for both functional assessment and evaluate safety of patient at hom
e)-
Supportive m
edications for symptom
atic managem
ent
Grade 1 (M
ild)P
eripheral Motor:
-A
symptom
atic; clinical or diagnostic observations only
-N
o intervention indicated
Peripheral Sensory:
Asym
ptomatic;loss of deep tendon
reflexes or paresthesia
Grade 2 (M
oderate)P
eripheral Motor:
Moderate sym
ptoms; lim
iting A
DLs
Peripheral Sensory:
Moderate sym
ptoms; lim
iting A
DLs
Grade 3 (Severe)
Peripheral M
otor:S
evere symptom
s; limiting self-
care AD
Ls; requires assistive devices
Peripheral Sensory:
Severe sym
ptoms; lim
iting self-care A
DLs
Grade 4 (Potentially Life-Threatening)
Peripheral M
otor:Life-threatening;urgent intervention indicated
Peripheral Sensory:
Life-threatening;urgent intervention indicated
Grade 5 (D
eath)
Nursing Im
plementation:
-C
ompare baseline assessm
ent;grade & docum
ent neuropathy and etiology (diabetic, medication, vascular, chem
otherapy)-
Early identification and evaluation of patient sym
ptoms
-E
arly intervention with lab w
ork and office visit if neuropathy symptom
ssuspected
RED FLAGS:
-G
uillain–Barré syndrome
-M
yasthenia gravis
*Steroid
taperinstructions/calendarasa
guidebutnotan
absolute-
Tapershouldconsiderpatient’s
currentsymptom
profile-
Close
follow-up
inperson
orbyphone,based
onindividualneed
&sym
ptomatology
-A
nti-acidtherapy
dailyas
gastriculcerprevention
while
onsteroids
-R
eviewsteroid
medication
sideeffects:m
oodchanges
(anger,reactive,hyperaware,euphoric,m
ania), increasedappetite,interrupted
sleep,oralthrush,fluidretention
-B
ealertto
recurringsym
ptoms
assteroids
taperdown
& reportthem
(tapermay
needto
beadjusted)
Long-term
high-dosesteroids:
-C
onsiderantimicrobialprophylaxis
(sulfamethoxazole/trim
ethoprim double dose M
/W/F; single dose if used
daily) or alternative if sulfa-allergic (e.g., atovaquone [Mepron
®]1500 mg po daily)
-C
onsideradditionalantiviraland antifungalcoverage-
Avoid
alcohol/acetaminophen
orotherhepatoxins
AD
Ls = activities of daily living
Copyright ©
2017 Melanom
a Nursing Initiative.
© 2017 The M
elanoma N
ursing Initiative. All rights reserved
ww
w.them
elanomanurse.org
Neuropathy Page 2 of 2
© 2017 The M
elanoma N
ursing Initiative. All rights reserved
ww
w.them
elanomanurse.org
Nephritis Page 1 of 3
Care Step Pathw
ay –N
ephritis(inflam
mation of the kidneys)
Nursing Assessm
ent
Look:-
Does the patient appear uncom
fortable?-
Does the patient look ill?
Grading Toxicity
Acute K
idney Injury, Elevated Creatinine
Definition: A disorder characterized by the acute loss of renal function and
is traditionally classified as pre-renal, renal, and post-renal.
Listen:-
Has there been change in urination? o
Urine color?
oFrequency?
-H
ow m
uch fluid is the patient taking in?-
Are associated sym
ptoms present?
oN
ausea?o
Headache?
oM
alaise? o
Lungedem
a?-
Are there
symptom
s concerning for:o
Urinary tract infection?
oP
yelonephritis? o
Worsening C
HF?
-A
re symptom
s limiting A
DLs?
-C
urrent or recent use of nephrotoxic medications
(prescribed and OTC
) other agents?o
NS
AID
so
Antibiotics
oC
ontrast media or other nephrotoxic agents
(contrastdye, aminoglycosides, P
PI)?
Recognize:
-Laboratory abnorm
alities (elevated creatinine, electrolyte abnorm
alities)-
Urinalysis abnorm
alities (casts)-
Abdom
inal or pelvic disease that could be causing sym
ptoms
-P
riorhistory of renal comprom
ise? -
Other im
mune-related adverse effects?
-P
resence of current or prior imm
une-mediated
toxicities,including rhabdomyolysis
-Is patient volum
e depleted?
Managem
ent
Overall Strategy
-Assess for other etiologies,such as infection
-Elim
inate potentially nephrotoxic medications
-Ensure adequate hydration daily
-Evaluate for progressive kidney/adrenal/pelvic m
etastases that may be contributing to kidney dysfunction
-Early intervention to m
aintain orimprove physical function and im
pact on QO
L
Mild elevation in creatinine (G
rade 1)-
Anticipate im
munotherapy to continue
-P
erform detailed review
of concomitant
medications (prescribed and O
TC),
herbals,vitamins,anticipating possible
discontinuation of nephrotoxic agents-
Avoid/m
inimize addition of nephrotoxic
agents,such as contrast media for
radiology tests -
Anticipate close m
onitoringofcreatinine
(i.e.,weekly)
-E
ducate patient/family on im
portance of adequate daily hydration
and set individualized
hydration goals-
Review
symptom
s to watch for w
ith patient and fam
ily and remem
ber to assess at subsequent visits
Moderate elevation in creatinine (G
rade 2)-
Ipilimum
abto be w
ithheldfor any G
rade 2event (until G
rade 0/1) and discontinued
for events persisting ≥6 weeks or inability to
reduce steroid dose to 7.5 mg prednisone/day
-P
embrolizum
ab or nivolumab to be w
ithheld for Grade 2 events
persisting ≥12 weeks or inability to reduce steroid dose to ≤10 m
g prednisone or equivalent per day
-A
nticipate increase in frequency of creatininem
onitoring (i.e.,every 2–3 days until im
provement)
-Im
munosuppressive
medications to be initiated to treat im
mune-
mediated nephritis o
System
ic corticosteroids (e.g.,prednisone)0.5–1 mg/kg/day
until symptom
improve to baseline follow
ed by slowtaper
over at least 1m
ontho
Anticipate increased
in corticosteroid dosing (i.e.,treat as if G
rade 3 nephritis) if creatinine does not improve w
ithin 48–72hours
oA
nticipate use of additional supportive care medications
-U
pon symptom
sresolution to patient’s baseline, orG
rade 1, begin
to tapercorticosteroid dose slowly over 1 m
onth-
Anticipatory guidance on proper adm
inistration -
Anticipate the use of IV
fluid to ensure adequate hydration-
Anticipate that nephrology consultation m
ay be initiated by provider
-A
ssess patient & fam
ily understanding of recomm
endations and rationale
-Identify barriers to adherence
Moderate (G
rade 3)and Severe (Grade 4)
-P
embrolizum
ab or nivolumab to be w
ithheld for first-occurrence G
rade 3/4 event anddiscontinued
if:o
Grade 3/4 event recurs
oP
ersists ≥12 weeks
oR
equires >10 mg prednisone or equivalent per day for m
ore than 12 w
eeks. -
Ipilimum
ab to be discontinued for any Grade 3/4 event
-Im
munosuppressive m
edications to be initiated to treat imm
une-m
ediated nephritiso
Corticosteroids (e.g., prednisone 1–2 m
g/kg/day, in divided doses)until sym
ptoms
improve to baseline and then slow
taper over at least 1
month
oIf sym
ptoms do not im
prove within 48–72 hours, additional
imm
unosuppressivem
edications will be considered
-A
nticipate nephrologyconsultation
will be initiated by provider
-A
nticipate that renal biopsy will be considered
-H
emodialysis m
ay be considered-
Anticipate possible hospital adm
ission for Grade 4 elevations in
creatinine or in patients with m
ultiple comorbidities
Grade 1 (M
ild)C
reatinine level >0.3 mg/dL;
creatinine 1.5–2×U
LN
Grade 2 (M
oderate)C
reatinine 2–3×U
LNG
rade 3 (Severe)C
reatinine >3×U
LN or > 4.0
mg/dL; hospitalization indicated
Grade 4 (Potentially Life-Threatening)
Life-threatening consequences; dialysis indicated
Grade 5
(Death)
Nursing Im
plementation:
-Identify
individualsw
ith pre-existing renal dysfunction prior to initiating imm
unotherapy. Ensure
baseline creatininehas been
obtained-
Check kidney function prior to each dose of im
munotherapy
-M
onitor creatinine more frequently if levels appear to be rising,and for G
rade 1 toxicity-
Educate patients that new urinary sym
ptoms
should be reported imm
ediately-
Anticipate the steroid requirements to m
anage imm
une-mediated nephritis are high
(up to 1 –2 mg/kg/d)and patients
will be on corticosteroid therapy for at least 1
month
-Educate patients and fam
ily about the rationale for discontinuation of imm
unotherapy in patients who develop severe nephritis
RED FLAGS:
-Risk of acute onset
-Risk of m
ortality if unrecognized or treatment is delayed
-Risk of im
mune-m
ediated nephritis is greater in patients receiving combination im
munotherapy regim
ens and PD-1 inhibitors -
In addition to acute interstitial nephritis seen from PD-1 inhibitors, there are case reports of lupus-like nephritis and granulom
atous acute interstitial nephritis
AD
Ls = activities of daily living; CH
F = congestiveheart failure; LE
= lung edema; N
SA
IDs
= nonsteroidal anti-inflamm
atory drugs; OTC
= over the counter; PP
I = proton pump inhibitor;
QO
L= quality of life; U
LN = upper lim
it of normal.
Copyright ©
2017 Melanom
a Nursing Initiative.
© 2017 The M
elanoma N
ursing Initiative. All rights reserved
ww
w.them
elanomanurse.org
Nephritis Page 2 of 3
Care Step Pathw
ay –N
ephritis(inflam
mation of the kidneys)
Nursing Assessm
ent
Look:-
Does the patient appear uncom
fortable?-
Does the patient look ill?
Grading Toxicity
Acute K
idney Injury, Elevated Creatinine
Definition: A disorder characterized by the acute loss of renal function and
is traditionally classified as pre-renal, renal, and post-renal.
Listen:-
Has there been change in urination? o
Urine color?
oFrequency?
-H
ow m
uch fluid is the patient taking in?-
Are associated sym
ptoms present?
oN
ausea?o
Headache?
oM
alaise? o
Lungedem
a?-
Are there
symptom
s concerning for:o
Urinary tract infection?
oP
yelonephritis? o
Worsening C
HF?
-A
re symptom
s limiting A
DLs?
-C
urrent or recent use of nephrotoxic medications
(prescribed and OTC
) other agents?o
NS
AID
so
Antibiotics
oC
ontrast media or other nephrotoxic agents
(contrastdye, aminoglycosides, P
PI)?
Recognize:
-Laboratory abnorm
alities (elevated creatinine, electrolyte abnorm
alities)-
Urinalysis abnorm
alities (casts)-
Abdom
inal or pelvic disease that could be causing sym
ptoms
-P
riorhistory of renal comprom
ise? -
Other im
mune-related adverse effects?
-P
resence of current or prior imm
une-mediated
toxicities,including rhabdomyolysis
-Is patient volum
e depleted?
Managem
ent
Overall Strategy
-Assess for other etiologies,such as infection
-Elim
inate potentially nephrotoxic medications
-Ensure adequate hydration daily
-Evaluate for progressive kidney/adrenal/pelvic m
etastases that may be contributing to kidney dysfunction
-Early intervention to m
aintain orimprove physical function and im
pact on QO
L
Mild elevation in creatinine (G
rade 1)-
Anticipate im
munotherapy to continue
-P
erform detailed review
of concomitant
medications (prescribed and O
TC),
herbals,vitamins,anticipating possible
discontinuation of nephrotoxic agents-
Avoid/m
inimize addition of nephrotoxic
agents,such as contrast media for
radiology tests -
Anticipate close m
onitoringofcreatinine
(i.e.,weekly)
-E
ducate patient/family on im
portance of adequate daily hydration
and set individualized
hydration goals-
Review
symptom
s to watch for w
ith patient and fam
ily and remem
ber to assess at subsequent visits
Moderate elevation in creatinine (G
rade 2)-
Ipilimum
abto be w
ithheldfor any G
rade 2event (until G
rade 0/1) and discontinued
for events persisting ≥6 weeks or inability to
reduce steroid dose to 7.5 mg prednisone/day
-P
embrolizum
ab or nivolumab to be w
ithheld for Grade 2 events
persisting ≥12 weeks or inability to reduce steroid dose to ≤10 m
g prednisone or equivalent per day
-A
nticipate increase in frequency of creatininem
onitoring (i.e.,every 2–3 days until im
provement)
-Im
munosuppressive
medications to be initiated to treat im
mune-
mediated nephritis o
System
ic corticosteroids (e.g.,prednisone)0.5–1 mg/kg/day
until symptom
improve to baseline follow
ed by slowtaper
over at least 1m
ontho
Anticipate increased
in corticosteroid dosing (i.e.,treat as if G
rade 3 nephritis) if creatinine does not improve w
ithin 48–72hours
oA
nticipate use of additional supportive care medications
-U
pon symptom
sresolution to patient’s baseline, orG
rade 1, begin
to tapercorticosteroid dose slowly over 1 m
onth-
Anticipatory guidance on proper adm
inistration -
Anticipate the use of IV
fluid to ensure adequate hydration-
Anticipate that nephrology consultation m
ay be initiated by provider
-A
ssess patient & fam
ily understanding of recomm
endations and rationale
-Identify barriers to adherence
Moderate (G
rade 3)and Severe (Grade 4)
-P
embrolizum
ab or nivolumab to be w
ithheld for first-occurrence G
rade 3/4 event anddiscontinued
if:o
Grade 3/4 event recurs
oP
ersists ≥12 weeks
oR
equires >10 mg prednisone or equivalent per day for m
ore than 12 w
eeks. -
Ipilimum
ab to be discontinued for any Grade 3/4 event
-Im
munosuppressive m
edications to be initiated to treat imm
une-m
ediated nephritiso
Corticosteroids (e.g., prednisone 1–2 m
g/kg/day, in divided doses)until sym
ptoms
improve to baseline and then slow
taper over at least 1
month
oIf sym
ptoms do not im
prove within 48–72 hours, additional
imm
unosuppressivem
edications will be considered
-A
nticipate nephrologyconsultation
will be initiated by provider
-A
nticipate that renal biopsy will be considered
-H
emodialysis m
ay be considered-
Anticipate possible hospital adm
ission for Grade 4 elevations in
creatinine or in patients with m
ultiple comorbidities
Grade 1 (M
ild)C
reatinine level >0.3 mg/dL;
creatinine 1.5–2×U
LN
Grade 2 (M
oderate)C
reatinine 2–3×U
LNG
rade 3 (Severe)C
reatinine >3×U
LN or > 4.0
mg/dL; hospitalization indicated
Grade 4 (Potentially Life-Threatening)
Life-threatening consequences; dialysis indicated
Grade 5
(Death)
Nursing Im
plementation:
-Identify
individualsw
ith pre-existing renal dysfunction prior to initiating imm
unotherapy. Ensure
baseline creatininehas been
obtained-
Check kidney function prior to each dose of im
munotherapy
-M
onitor creatinine more frequently if levels appear to be rising,and for G
rade 1 toxicity-
Educate patients that new urinary sym
ptoms
should be reported imm
ediately-
Anticipate the steroid requirements to m
anage imm
une-mediated nephritis are high
(up to 1 –2 mg/kg/d)and patients
will be on corticosteroid therapy for at least 1
month
-Educate patients and fam
ily about the rationale for discontinuation of imm
unotherapy in patients who develop severe nephritis
RED FLAGS:
-Risk of acute onset
-Risk of m
ortality if unrecognized or treatment is delayed
-Risk of im
mune-m
ediated nephritis is greater in patients receiving combination im
munotherapy regim
ens and PD-1 inhibitors -
In addition to acute interstitial nephritis seen from PD-1 inhibitors, there are case reports of lupus-like nephritis and granulom
atous acute interstitial nephritis
AD
Ls = activities of daily living; CH
F = congestiveheart failure; LE
= lung edema; N
SA
IDs
= nonsteroidal anti-inflamm
atory drugs; OTC
= over the counter; PP
I = proton pump inhibitor;
QO
L= quality of life; U
LN = upper lim
it of normal.
Copyright ©
2017 Melanom
a Nursing Initiative.
© 2017 The M
elanoma N
ursing Initiative. All rights reserved
ww
w.them
elanomanurse.org
Nephritis Page 3 of 3
Care Step Pathw
ay –N
ephritis(inflam
mation of the kidneys)
Nursing Assessm
ent
Look:-
Does the patient appear uncom
fortable?-
Does the patient look ill?
Grading Toxicity
Acute K
idney Injury, Elevated Creatinine
Definition: A disorder characterized by the acute loss of renal function and
is traditionally classified as pre-renal, renal, and post-renal.
Listen:-
Has there been change in urination? o
Urine color?
oFrequency?
-H
ow m
uch fluid is the patient taking in?-
Are associated sym
ptoms present?
oN
ausea?o
Headache?
oM
alaise? o
Lungedem
a?-
Are there
symptom
s concerning for:o
Urinary tract infection?
oP
yelonephritis? o
Worsening C
HF?
-A
re symptom
s limiting A
DLs?
-C
urrent or recent use of nephrotoxic medications
(prescribed and OTC
) other agents?o
NS
AID
so
Antibiotics
oC
ontrast media or other nephrotoxic agents
(contrastdye, aminoglycosides, P
PI)?
Recognize:
-Laboratory abnorm
alities (elevated creatinine, electrolyte abnorm
alities)-
Urinalysis abnorm
alities (casts)-
Abdom
inal or pelvic disease that could be causing sym
ptoms
-P
riorhistory of renal comprom
ise? -
Other im
mune-related adverse effects?
-P
resence of current or prior imm
une-mediated
toxicities,including rhabdomyolysis
-Is patient volum
e depleted?
Managem
ent
Overall Strategy
-Assess for other etiologies,such as infection
-Elim
inate potentially nephrotoxic medications
-Ensure adequate hydration daily
-Evaluate for progressive kidney/adrenal/pelvic m
etastases that may be contributing to kidney dysfunction
-Early intervention to m
aintain orimprove physical function and im
pact on QO
L
Mild elevation in creatinine (G
rade 1)-
Anticipate im
munotherapy to continue
-P
erform detailed review
of concomitant
medications (prescribed and O
TC),
herbals,vitamins,anticipating possible
discontinuation of nephrotoxic agents-
Avoid/m
inimize addition of nephrotoxic
agents,such as contrast media for
radiology tests -
Anticipate close m
onitoringofcreatinine
(i.e.,weekly)
-E
ducate patient/family on im
portance of adequate daily hydration
and set individualized
hydration goals-
Review
symptom
s to watch for w
ith patient and fam
ily and remem
ber to assess at subsequent visits
Moderate elevation in creatinine (G
rade 2)-
Ipilimum
abto be w
ithheldfor any G
rade 2event (until G
rade 0/1) and discontinued
for events persisting ≥6 weeks or inability to
reduce steroid dose to 7.5 mg prednisone/day
-P
embrolizum
ab or nivolumab to be w
ithheld for Grade 2 events
persisting ≥12 weeks or inability to reduce steroid dose to ≤10 m
g prednisone or equivalent per day
-A
nticipate increase in frequency of creatininem
onitoring (i.e.,every 2–3 days until im
provement)
-Im
munosuppressive
medications to be initiated to treat im
mune-
mediated nephritis o
System
ic corticosteroids (e.g.,prednisone)0.5–1 mg/kg/day
until symptom
improve to baseline follow
ed by slowtaper
over at least 1m
ontho
Anticipate increased
in corticosteroid dosing (i.e.,treat as if G
rade 3 nephritis) if creatinine does not improve w
ithin 48–72hours
oA
nticipate use of additional supportive care medications
-U
pon symptom
sresolution to patient’s baseline, orG
rade 1, begin
to tapercorticosteroid dose slowly over 1 m
onth-
Anticipatory guidance on proper adm
inistration -
Anticipate the use of IV
fluid to ensure adequate hydration-
Anticipate that nephrology consultation m
ay be initiated by provider
-A
ssess patient & fam
ily understanding of recomm
endations and rationale
-Identify barriers to adherence
Moderate (G
rade 3)and Severe (Grade 4)
-P
embrolizum
ab or nivolumab to be w
ithheld for first-occurrence G
rade 3/4 event anddiscontinued
if:o
Grade 3/4 event recurs
oP
ersists ≥12 weeks
oR
equires >10 mg prednisone or equivalent per day for m
ore than 12 w
eeks. -
Ipilimum
ab to be discontinued for any Grade 3/4 event
-Im
munosuppressive m
edications to be initiated to treat imm
une-m
ediated nephritiso
Corticosteroids (e.g., prednisone 1–2 m
g/kg/day, in divided doses)until sym
ptoms
improve to baseline and then slow
taper over at least 1
month
oIf sym
ptoms do not im
prove within 48–72 hours, additional
imm
unosuppressivem
edications will be considered
-A
nticipate nephrologyconsultation
will be initiated by provider
-A
nticipate that renal biopsy will be considered
-H
emodialysis m
ay be considered-
Anticipate possible hospital adm
ission for Grade 4 elevations in
creatinine or in patients with m
ultiple comorbidities
Grade 1 (M
ild)C
reatinine level >0.3 mg/dL;
creatinine 1.5–2×U
LN
Grade 2 (M
oderate)C
reatinine 2–3×U
LNG
rade 3 (Severe)C
reatinine >3×U
LN or > 4.0
mg/dL; hospitalization indicated
Grade 4 (Potentially Life-Threatening)
Life-threatening consequences; dialysis indicated
Grade 5
(Death)
Nursing Im
plementation:
-Identify
individualsw
ith pre-existing renal dysfunction prior to initiating imm
unotherapy. Ensure
baseline creatininehas been
obtained-
Check kidney function prior to each dose of im
munotherapy
-M
onitor creatinine more frequently if levels appear to be rising,and for G
rade 1 toxicity-
Educate patients that new urinary sym
ptoms
should be reported imm
ediately-
Anticipate the steroid requirements to m
anage imm
une-mediated nephritis are high
(up to 1 –2 mg/kg/d)and patients
will be on corticosteroid therapy for at least 1
month
-Educate patients and fam
ily about the rationale for discontinuation of imm
unotherapy in patients who develop severe nephritis
RED FLAGS:
-Risk of acute onset
-Risk of m
ortality if unrecognized or treatment is delayed
-Risk of im
mune-m
ediated nephritis is greater in patients receiving combination im
munotherapy regim
ens and PD-1 inhibitors -
In addition to acute interstitial nephritis seen from PD-1 inhibitors, there are case reports of lupus-like nephritis and granulom
atous acute interstitial nephritis
AD
Ls = activities of daily living; CH
F = congestiveheart failure; LE
= lung edema; N
SA
IDs
= nonsteroidal anti-inflamm
atory drugs; OTC
= over the counter; PP
I = proton pump inhibitor;
QO
L= quality of life; U
LN = upper lim
it of normal.
Copyright ©
2017 Melanom
a Nursing Initiative.
APPENDIX 2
© 2017 The Melanoma Nursing Initiative. All rights reserved www.themelanomanurse.org
© 2017 The Melanoma Nursing Initiative. All rights reserved www.themelanomanurse.org
Inspired By Patients . Empowered By Knowledge . Impacting Melanoma
Adverse event Common symptoms Common management/anticipatory guidance
Acute respiratory distress syndrome
Severe shortness of breath, dyspnea, or rapid breathing, hypotension, confusion, and extreme fatigue
• Serious condition requiring hospitalization/expert care, including supplemental oxygen, often mechanical ventilation, and fluid management
Anorexia Decreased appetite
• Monitor weight; query patient about appetite/eating habits; advise dietary modification if necessary. (should improve with time)
• Anticipate standard dose holds/discontinuations*• Consider referral to nutrition services for counseling on best food
choices to avoid excessive weight loss
Cardiotoxicity: cardiomyopathy, myocarditis, heart failure
Dyspnea, edema, fatigue, chest pain, arrhythmias, abdominal pain or ascites
• Monitor weight, changes in breathing, extremity edema, chest/back/arm/jaw pain, pressure
• ECG, Echo, stress test cardiology referral, 2 mg/kg prednisone, discontinue therapy
Constipation/abdominal pain (associated with nivolumab)
Infrequent stools/difficulty stooling, abdominal pain
• Increase fluid, fiber; use caution with use of laxatives• Consider appropriate testing to evaluate bowel obstruction• Anticipate standard nivolumab dose holds/discontinuations* for
Grade 3 and Grade 4 (constipation with manual evacuation indicated, severe abdominal pain, or life-threatening consequences)
Embryo-fetal toxicity ––
• Advise of risk to fetus and recommend use of effective contraception during treatment and for 3 months after ipilimumab and for 5 months after nivolumab is discontinued
• Advise patient to tell HCP immediately if they or their partner suspect they are pregnant while taking therapy
Encephalitis
Headache, fever, tiredness, confusion, memory problems, sleepiness, hallucinations, seizures, stiff neck
• New-onset (Grade 2-3) moderate to severe symptoms: rule out infectious or other causes; consult neurologist, obtain brain MRI and lumbar puncture
• For ipilimumab: Anticipate standard ipilimumab dose holds/discontinuations;* administer corticosteroids at dose of 1-2 mg/kg/d prednisone equivalents (or 2-4 mg/kg if necessary)
• For nivolumab: Withhold nivolumab for new-onset moderate to severe neurologic symptoms; evaluate as described above; if other etiologies are ruled out, administer corticosteroids and permanently discontinue nivolumab for immune-mediated encephalitis
Management of other AEs associated with nivolumab/ipilimumab therapy.
© 2017 The Melanoma Nursing Initiative. All rights reserved www.themelanomanurse.org
Inspired By Patients . Empowered By Knowledge . Impacting Melanoma
Adverse event Common symptoms Common management/anticipatory guidance
Fatigue Feeling tired; lack of energy
• Query patients regarding energy level; evaluate possible contributory factors, including infection, disease progression, and hematological and metabolic abnormalities; standard supportive care
• Anticipate standard dose holds/discontinuations*• Fatigue that interferes with ADLs is concerning and should be
evaluated for underlying causes
Headache Head pain
• Need to rule out brain metastases, encephalitis, or hypophysitis; otherwise, standard supportive care (should improve with time)
• Headache occurring in conjunction with fatigue could be indicative of hypophysitis
• Anticipate standard dose holds/discontinuations*
Infusion reaction
Chills/shaking, back pain, itching, flushing, difficulty breathing, hypotension, fever
• Nivolumab and/or ipilimumab: For mild/moderate (Grade 1-2) reactions: interrupt or slow rate of infusion; monitor to recovery
• For severe/life-threatening (Grade 3-4) reactions: Discontinue nivolumab and/or ipilimumab; manage anaphylaxis via institutional protocol; monitor. Premedication with an antipyretic and antihistamine may be considered for future doses
Insomnia (associated with ipilimumab and corticosteroid therapy)
Difficulty falling or staying asleep
• Counsel patients on good sleep habits; prescription medications can be used if needed (should improve over time)
• Anticipate standard dose holds/discontinuations*
Nausea/vomiting Vomiting, queasiness, RUQ or LUQ pain
• May indicate hepatotoxicity; check LFTs/lipase/amylase; standard supportive care
• Anticipate dose holds/discontinuations*
Ocular: conjunctivitis, blepharitis, episcleritis, iritis, ocular myositis, scleritis, uveitis (associated with ipilimumab)
Blurry vision, double vision, or other vision problems, eye pain or redness
• Encourage patient to report any eye symptoms immediately• Obtain ophthalmology referral• Anticipate standard dose ipilimumab holds/discontinuations*
Management of other AEs associated with nivolumab/ipilimumab therapy. (Continued)
© 2017 The Melanoma Nursing Initiative. All rights reserved www.themelanomanurse.org
Inspired By Patients . Empowered By Knowledge . Impacting Melanoma
Adverse event Common symptoms Common management/anticipatory guidance
Pyrexia Elevated body temperature
• Standard supportive care related to cytokine release• Consider infectious workup for prolonged elevated temperature• Anticipate standard dose holds/discontinuations*
Rhabdomyolysis
Pain, muscle weakness, vomiting, confusion, tea-colored urine
• Anticipate dose holds/discontinuations*
• Intravenous fluids and corticosteroids (check creatine kinase levels)
Upper respiratory tract infection
Cough, runny nose, sore throat, nasal breathing
• Standard supportive care• Any cough needs to be evaluated for possible infection vs
pneumonitis• Anticipate standard nivolumab treatment holds*
*Dose holds/discontinuationsFor nivolumab: Withhold for any Grade 3 (severe) AE. Permanently discontinue for any Grade 4 (life-threatening) AE, persistent Grade 2-3 AE, any severe (Grade 3) AE that recurs, or when ≥10 mg/d prednisone or equivalent is required for 12 weeks. Resume treatment when AE returns to Grade 0 or 1.For ipilimumab: Withhold for any Grade 2 (moderate) AE, and resume treatment when AE returns to Grade 0 or 1; permanently discontinue for any Grade 3-4 (life-threatening) AE, persistent Grade 2 AE lasting ≥6 weeks, or inability to reduce corticosteroid dose to 7.5 mg/d prednisone or equivalent.
Management of other AEs associated with nivolumab/ipilimumab therapy. (Continued)