Value-Based Care: In Multiple Myeloma

Value-BasedCareIN MulTIPlE MyEloMA

™

Side Effect Management in theTreatment of Multiple Myeloma Introduction

The incorporation of novel therapies into thetreatment paradigm for multiple myeloma (MM)has extended survival and improved the lives ofpatients. Individuals treated with newer therapiesare surviving approximately 50% longer than sim-ilar patient populations treated with older regi-mens 10 years ago.1 The proteasome inhibitor bor -tezomib and the immunomodulators thalidomideand lenalidomide have demonstrated striking effi-cacy in clinical trials, and their inclusion in treat-ment regimens is now an evidence-based standardof care for the disease. The increased use of autol-ogous stem cell transplant (ASCT) has also result-ed in prolonged survival in myeloma patients.2,3

However, these dramatic improvements havecome at a cost: the use of novel agents and ASCT

has substantially increased the economic burdenassociated with myeloma care. Two recent presen-tations described estimates of the overall costsassociated with treatment.4,5 One study compared18 regimens and found considerable variations inboth the weekly cost of treatment ($766-$4940)and the overall response rate (ORR) (39%-92%).The weekly cost per ORR ranged from $957 fortreatment with a regimen of bortezomib, dexa-methasone, and doxorubicin to $8821 for a regi-men of bortezomib, melphalan, prednisone, andthalidomide.4 The other study compared the in -cremental cost-effectiveness over a 20-year life-time horizon of 2 myeloma regimens: bortezomib,melphalan, and prednisone (VMP) and melpha-lan, prednisone, and lenalidomide plus continu-ous lenalidomide maintenance (MPR-R).5 For

An official publication of

EDITORIALADVISORY BOARD

Leon H. Dragon, MD, FACPMedical DirectorKellogg Cancer CenterNorthshore University HealthSystemClinical Assistant Professor of MedicineUniversity of Chicago Pritzker School of Medicine

Charles M. Farber, MD, PhDSection Chief of Hematology and OncologyDepartment of MedicineCarol G. Simon Cancer Center

Jonathan L. Kaufman, MDAssistant Professor of Hematologyand OncologyWinship Cancer Institute of Emory University

James T. Kenney Jr, RPh,MBAPharmacy Operations ManagerHarvard Pilgrim Health Care, Inc

Ira Klein, MD, MBA, FACPMedical DirectorAetna Pharmacy Management

Noopur S. Raje, MDAssistant Professor of MedicineHarvard Medical SchoolDirector, Center for Multiple MyelomaMassachusetts General Hospital

G. David Roodman, MD, PhDProfessor, University of PittsburghSchool of MedicineDirector, Bone Biology CenterUniversity of Pittsburgh Medical Center

Winston Wong, PharmDAssociate Vice PresidentPharmacy ManagementCareFirst BlueCross BlueShield

EDITOR’S NOTE

SEPTEMBER 2011 ◆ 4th IN A 6-PART SERIES

This newsletter has

been supported by

funding from

Millennium

Pharmaceuticals, Inc.

With the goal of promoting a better understanding of the relationship between cost and clin-ical outcomes, the Association for Value-Based Cancer Care® is publishing a newsletter series toaddress various aspects of value-based care for patients with multiple myeloma (MM). Thesepub lications report on the latest clinical updates pertaining to the management of the dis-ease, and provide stakeholder perspectives on how these data can be used to promote high-qual-ity, cost-effective care. Previous newsletters in this series (available at www.AVBCConline.org)discussed therapeutic choices based on the presence of high-risk cytogenetic abnormalities, the rel-evance of end points in clinical trials for MM, and the impact of novel agents on myeloma-asso-ciated renal impairment. In this fourth issue, we will focus on the value of incorporating best prac-tices for managing treatment-related toxicities. Subsequent issues will address the potentialeconomic implications of novel agents used to treat myeloma-related bone complications andvalue-based benefit design considerations for the disease.

S T A K E H O L D E R S ’ P E R S P E C T I V E S

Value-Based Approach to Managing Adverse Events in Myeloma.....................................................9Atheer A. Kaddis, PharmD

Preventing and Treating Peripheral Neuropathy in Myeloma ...........................................................10Stephanie S. Minich, PharmD, BCOP

this comparison, investigators used response and survival datafrom the phase 3 VISTA trial, which compared melphalanand prednisone (MP) with VMP, and the MM-015 trial,which compared MP with MPR-R. Costs included per-proto-col drug and medical costs, treatment-related toxicities, sec-ond-line therapy, and resource utilization. In the VISTA trial,VMP provided a survival benefit over MP (hazard ratio[HR]=0.65), whereas in MM-015, MPR-R showed no survivalbenefit over MP (median follow-up, 21 months). Estimatedoverall survival (OS) was 4.187 years with VMP and 3.409years with MPR-R over a lifetime horizon. Lifetime directmedical costs for these regimens were $119,102 and $241,247,respectively. In terms of OS, it was determined that MPR-Rwould become cost-effective only at an HR of £0.25 com-pared with MP.5

In addition to drug acquisition and provision of transplantservices, other factors must be considered when assessing thecosts associated with MM treatment. For example, novelagents have distinct toxicity profiles that may raise utilizationcosts related to provider services and medications required totreat adverse events (AEs). These toxicities may also have anegative effect on productivity and health-related quality oflife (HRQOL). In addition, ASCT can lead to severe myelo-suppression and other complications, thereby increasing theincidence and length of hospitalization and the need for ancil-lary services ranging from growth-factor support to psycho-behavioral interventions. Given the proven efficacy of novelagents in the frontline setting, investigators are now question-ing whether ASCT can be delayed in some cases until thetime of relapse.6 This issue remains a subject of ongoing debateand will continue to be investigated in clinical trials.

In today’s healthcare environment, it is important to ana-lyze all aspects of disease management—including the cost ofpreventing and minimizing AEs—when making value-baseddecisions regarding care. Therefore, the safety profiles ofbortezomib, thalidomide, and lenalidomide must be consid-ered in any economic evaluation of myeloma treatment. Thisarticle discusses some of the major AEs associated with eachof these novel agents, along with prevention and manage-ment strategies and related cost considerations.

BortezomibIn clinical trials evaluating bortezomib as monotherapy for

the treatment of myeloma, major AEs that emerged were neu-rotoxicity and myelosuppression.7-12 When this agent wascompared with high-dose dexamethasone in the relapsed set-ting, common grade 3 or 4 AEs reported in bortezomib-treat-

ed patients were thrombocytopenia (30%), neutropenia (14%),and peripheral neuropathy (PN) (8%).10 In 2 studies of bor -tezomib plus dexamethasone in relapsed or refractory MM,the incidence and type of toxicities were similar to those seenin trials of bortezomib alone.7,13

In the VISTA trial of newly diagnosed, transplant-ineligi-ble patients with MM,14 myelosuppression was similar in the2 groups, but neurotoxicity was more common with VMPthan with MP (44% vs 5%, respectively). However, the PNwas reversible in 74% of patients; it resolved in 56% ofpatients and decreased by 1 or more grades in 18% of patientswithin a median of 2 months. Grade 3 or 4 gastrointestinaltoxicities were also more common in the VMP group than inthe MP group (19% vs 5%, respectively). Similarly, the inci-dence of any grade of herpes zoster was higher in patientsreceiving bortezomib than in those receiving MP alone (13%vs 4%, respectively), although viral prophylaxis was notrequired in this trial and many patients did not receive it.

Managing bortezomib-associated myelosuppressionBortezomib-associated thrombocytopenia and neutropenia

follow a cyclical pattern. Platelet and neutrophil nadirs occurafter the last dose of each treatment cycle; counts typicallyrecover prior to the start of the next cycle. Platelet counts ofpatients receiving bortezomib twice weekly decrease duringeach 21-day cycle of treatment and reach a nadir of about40% of baseline following the last dose of each cycle.15 Noevidence of cumulative thrombocytopenia or neutropenia hasbeen observed in clinical trials. Platelet and neutrophil countsshould be monitored and dose-adjusted when needed to ame-liorate the degree of myelosuppression; if necessary, a transfu-sion may be considered.15-17 Cost drivers for thrombocytope-nia and neutropenia include nursing and pharmacy timeneeded for dose adjustments and patient counseling, andtreatment modalities such as transfusions and growth-factorsupport. In cases of neutropenia-related infection, treatmentwith antimicrobial agents as well as office, emergency, andhospital visits must also be considered.18

Managing bortezomib-induced neuropathyIn clinical trials of bortezomib in the relapsed MM setting,

baseline neuropathy has been documented in some patients;this may be due to the prior use of neurotoxic agents such asvincristine, cisplatin, and thalidomide.19 Neuropathy mayalso be caused by the myeloma itself, and approximately 3%to 13% of patients present with this condition at the time ofdiagnosis, prior to the initiation of therapy.20 However, the

2 ◆ September 2011 www.AVBCConline.org

Novel agents have distinct toxicity profiles that may raise utilization costs related to

provider services and medications required to treat adverse events.

In today’s healthcare environment, it is important to analyze all aspects of disease management when making

value-based decisions regarding care.

inclusion of bortezomib may exacerbatethe risk of this toxicity. In newly diagnosedMM patients initially treated with bor -tezomib in clinical trials, grades 1 and 2neuropathy affected approximately 24% to33% of patients, whereas grades 3 and 4 PNdeveloped in up to 18% of patients.19,21

Age is a major risk factor for the devel-opment of bortezomib-induced peripheralneuropathy (BIPN); this risk increasesabout 6% per year of advancing age.22

Other risk factors identified in clinical tri-als include therapy duration, dose intensi-ty, cumulative dose, comorbid conditions(eg, diabetes mellitus, alcoholism), and thepresence of preexisting neuropathy.23 Arecent subanalysis of the VISTA trial, how-ever, found that the only consistent risk factor for PN wasbaseline neuropathy.21

Bortezomib appears to induce neurotoxicity via axonal de -generation.24,25 This often occurs within the first cycle oftreatment and does not seem to increase after the fifth cycle.26

In the VISTA trial, the median time to onset of PN was 2.3months.21 BIPN usually begins as a sensory phenomenon,with numbness or tingling in the upper and lower extremities,or as a sensation of burning or cold.26 Sometimes, it progress-es to neuropathic pain, with painful shooting or crampingsensations. Another neuropathic manifestation associatedwith bortezomib is autonomic dysfunction, resulting inhypotension and gastrointestinal toxicities, such as diarrhea,nausea, and constipation.23

The incidence of PN may be reduced by replacing conven-tional twice-weekly intravenous (IV) dosing with alternativedosing strategies. In a recent phase 3 trial, administering IVbortezomib once per week reduced the incidence of grade 3 or4 PN to 8% (compared with 28% in patients receiving twice-weekly dosing). Efficacy was essentially the same for bothgroups.27 Administering bortezomib as a subcutaneous (SC)injection also appears to be effective for reducing the inci-dence of neuropathy without sacrificing therapeutic benefit.In a recent clinical trial, SC dosing was shown to be noninfe-rior to IV dosing on efficacy end points.28

The neurotoxic effects of bortezomib are generally re -versible with dose reduction or treatment discontinuation.According to a subanalysis of the VISTA trial, 79% of neuro-pathic events improved by at least 1 grade within a median of1.9 months; 60% of events completely resolved within amedian of 5.7 months.21 The dose of bortezomib should be ad -justed according to recommendations in the prescribing infor-mation, which are based on severity and degree of associatedneuropathic pain or impaired function (Table 1).15 The ben-efits of dose modification have been shown in a phase 3 trialof single-agent bortezomib, with resolution or improvementof grade 2 or higher PN observed in 68% of patients whounderwent a prespecified dose-reduction protocol, comparedwith 47% of those who did not.29

Nonpharmacologic management of sensory PN and neuro-pathic pain may include the use of daily vitamins, nutritionalsupplements, topical therapies, and physical manipulation.Vitamins and supplements include certain B vitamins (B1, B6,B12), folic acid, magnesium, potassium, vitamin E, acetyl L-car-nitine, �alpha-lipoic acid, and L-glutamine. Topical and physi-cal interventions include emollient creams (eg, cocoa butter,menthol, and eucalyptus-based creams), physical therapy, andtherapeutic massage.23,30 These recommendations are basedon anecdotal evidence and have not been confirmed in clin-ical trials. Pharmacologic therapy for PN includes gabapentin,pregabalin, nortriptyline, duloxetine, and topical lidocaine,based on short-term studies in other indications such as post -her petic neuralgia and painful diabetic neuropathy.23,30

Although it is certainly advantageous to have several op -tions to manage BIPN, most interventions are associated withadditional expenses. Nursing and pharmacy time, costs fordrugs and supplements to control neuropathic symptoms, andfees for massages, physical therapy, and assistive devices allcontribute to the economic burden. Moreover, neuropathicsymptoms can interfere with dressing, writing, keyboarding,household chores, ambulation, and many other activities ofdaily living that affect HRQOL and work productivity. Datasuggest that an event of therapy-related PN induced by anychemotherapy drug (bortezomib included) costs approximate-ly $4900 in lost productivity and at-home care.31

Managing bortezomib-associated varicella zoster virusTreatment with bortezomib is also associated with reactiva-

tion of varicella zoster virus (VZV). An analysis of data from

Value-Based Care in Multiple Myeloma ◆ 3

Table 1. Recommended Bortezomib Dose Modifications15

Severity of Peripheral Neuropathy Modification of Dose and Regimen

Grade 1 (paresthesia or loss of reflex)without pain or loss of function

Grade 1 with pain or grade 2 (interferes with function but not with activities of daily living)

Grade 2 with pain or grade 3 (interferes with activities of daily living)

Grade 4 (permanent sensory loss that interferes with function)

No action

Reduce bortezomib dose from 1.3to 1.0 mg/m2

Withhold bortezomib until toxicity resolves, then reinitiate at a doseof 0.7 mg/m2 once weekly

Discontinue bortezomib

Administering bortezomib as a subcutaneousinjection also appears to be effective

for reducing the incidence of neuropathy without sacrificing therapeutic benefit.

a phase 3 clinical trial of relapsed/refractory MM demonstrat-ed that bortezomib treatment resulted in a significantly in -creased incidence of VZV reactivation compared with high-dose dexamethasone (13% vs 5%, respectively).32 Most VZVinfections were grade 1 or 2, and the incidence of grade 3 or4 infections was similar in bortezomib- and dexamethasone-treated patients (1.8% vs 1.5%, respectively). Patients receiv-ing bortezomib should be monitored for virus reactivation,and should be prescribed acyclovir as prophylaxis.33 Acycloviris available as a relatively inexpensive generic formulation,34

enhancing the value of prophylaxis. Antiviral prophylaxis isalso valuable because it prevents the costs and diminishedHRQOL associated with a painful herpes zoster infection andpostherpetic neuralgia.

LenalidomideTwo major AEs associated with lenalidomide use in pa -

tients with relapsed or refractory MM are myelosuppressionand venous thromboembolism (VTE). Pooled data from 2studies comparing lenalidomide plus dexamethasone withdexamethasone alone reported the following rates of grade 3or 4 AEs: neutropenia (35%), anemia (11%), thrombocyto -penia (13%), infection (16%), and VTE (13%).35,36 Similartoxicity profiles have been reported in other studies of lena -lidomide-based combination regimens.37-40 In patients treatedwith lenalidomide plus dexamethasone, grade 3 or 4 VTEranged from 3% to 26%, depending on whether they receivedthromboprophylaxis.41

Toxicities (with the exception of grade 3 or 4 neutropenia)

were significantly reduced in the ECOG E4A03 study ofnewly diagnosed MM patients that compared a standard reg-imen of lenalidomide plus high-dose dexamethasone withlenalidomide plus low-dose dexamethasone.42 Thrombopro -phylaxis was recommended but not mandated until late in thestudy. Grade 3 or 4 deep vein thrombosis (DVT) occurred in12% of patients treated with low-dose dexamethasone com-pared with 26% of patients assigned to high-dose dexametha-sone (Figure).

Managing lenalidomide-associated VTEAspirin, warfarin, and low-molecular-weight heparin

(LMWH) have all been used for routine thromboprophylaxisin lenalidomide-treated patients, but it has not been deter-mined whether this approach reduces the incidence of throm-boembolic events.43 The decision to use thromboprophylaxismust be based on the anticipated risk of thrombosis in theindividual patient. Prophylactic agents should be used onlywhen necessary, since they present additional serious risks,notably bleeding and hemorrhagic stroke.44 For example, be -cause lenalidomide alone does not induce a high risk of VTE,thromboprophylaxis is not recommended when lenalidomideis used as monotherapy.45

Cost of prophylaxis is not prohibitive, but the expense asso-ciated with treatment of DVT and pulmonary embolismincreases the overall cost of lenalidomide-based therapy.Hospitalization and treatment for an index episode of DVThas been estimated at greater than $20,000 in 2002 dollars.46 IfVTE does occur, rapid intervention may help reduce compli-cations that increase the cost of care. Therefore, patients andcaregivers should be educated on the signs of this toxicity andinstructed to seek treatment promptly if symptoms arise.

Managing lenalidomide-associated myelosuppressionMyelosuppression is a serious AE associated with lenalido-

mide.44,47 When platelet counts fall to <30,000/mcL, lenalido-mide treatment should be halted. Treatment may be resumedwhen platelet counts return to ≥30,000/mcL at a dose reducedfrom the standard 25 mg/day to 15 mg/day.44 When neu-trophil counts fall to <1000/mcL, lenalidomide treatmentshould be halted and granulocyte colony-stimulating factor(G-CSF) should be added. Lenalidomide treatment maycontinue at 25 mg/day when neutrophil counts return to≥1000/mcL, provided neutropenia is the only toxicity;lenalidomide should be restarted at 15 mg/day on return to≥1000/mcL in the presence of any additional toxicity. Foreach subsequent drop in the neutrophil count <1000/mcL,lenalidomide should be interrupted and resumed when the

Figure. Incidence of all AEs and DVT in the ECOGE4A03 trial of RD versus Rd.42


Pati

ents

(%

)

60

50

40

30

20

10

0

All AEs DVT

RD

Rd

AEs indicates adverse events; DVT, deep vein thrombosis; ECOG, EasternCooperative Oncology Group; Rd, lenalidomide plus low-dose dexamethasone; RD, lenalidomide plus high-dose dexamethasone.

All between-group differences were statistically significant (P£.04).

The expense associated with treatment of DVT and pulmonary embolism

increases the overall cost of lenalidomide-based therapy.

count returns to ≥1000/mcL, using a doseof 5 mg less than the previous dose to aminimum of 5 mg/day total dose.44 Anemiacan be managed with erythropoiesis-stimu-lating agents (ESAs), which are only rec-ommended when hemoglobin levels fall to<9 g/dL, especially in patients with cardiacdisease. For patients without cardiac dis-ease, ESAs may increase the risk of VTEand should be used with caution. The useof these agents (as well as G-CSFs) mayadd substantially to the cost of lenalido-mide treatment.

ThalidomideMajor grade 3 or 4 AEs associated with

thalidomide use include constipation, neu-ropathy, somnolence, depression, and VTE. A trial evaluatingsingle-agent thalidomide in relapsed or refractory MM report-ed that most AEs were mild or moderate and dose depend-ent.48 At a dose of 200 mg, approximately 25% of patients hadno appreciable toxicities, but at higher doses virtually allpatients experienced grade 1 or 2 toxicities. Less than 5% ofpatients reported grade 1 or 2 leukopenia at any dose.48 A sys-tematic review of clinical trials of single-agent thalidomideshowed that the most frequent grade 3 or 4 AEs were consti-pation (16%), somnolence (11%), neuropathy (6%), rash(3%), VTE (3%), and cardiac toxicity (2%).49 When thalido-mide is combined with other agents, the incidence of AEstends to increase. In a recent review of 12 trials of thalido-mide plus dexamethasone (TD) in patients with relapsed orrefractory MM, the major AEs were constipation (37%), neu-ropathy (27%), somnolence (26%), depression (10%), andVTE (5%).50 Among patients with newly diagnosed MM,combining thalidomide with other agents appears to increasesevere toxicities associated with thalidomide, including con-stipation, neuropathy, somnolence, and VTE. These combi-nations include: TD51-53; thalidomide, cyclophosphamide, anddexamethasone54; thalidomide, doxorubicin, dexamethasone,and melphalan55; thalidomide, melphalan, and prednisone56-59; and thalidomide, vincristine, liposomal doxorubicin, anddexamethasone.60

Managing thalidomide-induced neuropathyThalidomide-induced peripheral neuropathy (TIPN) is a

common and potentially serious AE.61 Half of all patientstreated with thalidomide experience distal sensory PN evenwith low doses (25-50 mg); in some studies up to 80% ofpatients developed neuropathy, with the frequency of grade 3or 4 events ranging from 3% to >15%.47 TIPN is cumulativeand dose dependent, and is therefore managed with dose re -duction or discontinuation (Table 2).61 Patients should bemonitored for early signs of neuropathy, particularly duringthe first 3 months of treatment.61 If symptoms develop,thalidomide should be discontinued immediately to limit fur-ther damage, if clinically appropriate.61 Usually, thalidomide

should be reinitiated only if the neuropathy returns to base-line status. TIPN may be reversible in some cases, but symp-toms tend to resolve slowly; this agent is known to cause per-manent nerve damage and irreversible neuropathy in somecases.61-63 When neuropathy is sustained, economic burdencan be high; productivity and activities of daily living areaffected permanently; and there may be a need for ongoingpharmacologic and nonpharmacologic interventions.

Managing thalidomide-associated VTEVTE is a serious toxicity observed in MM patients treated

with thalidomide in combination with anthracyclines anddexamethasone.64 In a trial of newly diagnosed patients whoreceived induction chemotherapy plus dexamethasone withor without thalidomide, DVT developed in 28% of patientswho received thalidomide, compared with just 4% of patientswho did not.65 All DVT episodes occurred within the first 3induction cycles, and thalidomide was safely resumed in 75%of patients receiving anticoagulation therapy.

Low-dose aspirin, warfarin, and LMWH are currently rec-ommended as thromboprophylaxis for patients receivingthalidomide.45,66-69 All 3 agents can be effective, but more re -search is needed to determine which prophylactic strategywill consistently reduce the risk of VTE to a goal of <10% ofpa tients.45 An expert panel has recommended LMWH(equivalent to enoxaparin 40 mg/day) or full-dose warfarin(international normalized ratio 2-3) for thalidomide- andlenalidomide-treated patients with ≥2 individual or myelo-ma-related risk factors, and for all patients receiving concur-rent high-dose dexamethasone, doxorubicin, or multiagentche motherapy (Table 3).45 There are incremental cost differ-


Table 2. Recommended Thalidomide Dose Modifications61

Severity of Peripheral Neuropathy Modification of Dose and Regimen

Grade 1 (mild)

Grade 1 with pain or grade 2

Grade 3

Grade 4 (permanent sensory loss thatinterferes with function)

No action

Intermittent symptoms:Continue therapyContinuous symptoms:Withhold thalidomide until toxicityresolves, then reduce dose

Withhold thalidomide until toxicityresolves then restart at reduced dose

Discontinue thalidomide

Low-dose aspirin, warfarin, and LMWH are currently recommended as thromboprophylaxis for patients

receiving thalidomide.

ences between LMWH and the older anticoagulant warfarinthat need to be considered. Pharmacoeconomic comparisonsof LMWH and warfarin for prophylaxis in a noncancer set-ting suggest that outcomes, administration costs, and the needfor frequent laboratory monitoring of warfarin are factors thatshould be analyzed in addition to drug price in determiningrelative cost of care.70 Aspirin, an inexpensive over-the-counter agent, can be used as prophylaxis for the subset ofthalidomide-treated patients with £1 risk factor for VTE.45

Managing thalidomide-associated neutropeniaThe use of thalidomide is associated with mild neutropenia

in 3% to 15% of patients. This rate increases when thalidomideis combined with other drugs, particularly myelotoxic agents.16

Given the risk of infection, patients receiving thali domideshould be closely monitored with repeat differential and wholeblood counts. If absolute neutrophil count (ANC) falls to<750/mcL, thalidomide should be re-evaluated and, if the neu-tropenia persists, consideration should be given to withholdingtreatment with this agent if clinically appropriate.61 The addi-tion of growth-factor support or a 50% dose reduction shouldbe considered for those with an ANC of 500/mcL to 1000/mcL;therapy should be discontinued immediately when this falls to<500/mcL.71 Thalidomide may be re started at a 50% lower dosewith or without growth-factor support once neutropenia re -solves.71 Other hematologic com plications, including anemia,leukopenia, and thrombocytopenia, are rarely associated withthis agent.71,72

ConclusionOver the past decade, advances in MM

therapy have improved outcomes as well asincreased the cost of care. In addition toacquisition and service charges for antimyelo-ma treatment, other key cost drivers exist,including the impact of treatment-relatedtoxicities on utilization, patient productivity,and HRQOL. The potential costs associatedwith serious AEs such as PN, infection due tomyelosuppression, and VTE must be factoredinto any balanced economic assessment ofmyeloma care.46 Value-based treatment requirescareful analysis of the total economic burdenlevied by each treatment option, including allcontributors to direct and indirect costs. Suchan analysis may reveal that the cost of a drug orservice is justified by better overall outcomes aswell as savings that accrue when AEs are pre-vented and managed effectively. ■

References1. Kumar SK, Rajkumar SV, Dispenzieri A, et al. Im -proved survival in multiple myeloma and the impact ofnovel therapies. Blood. 2008;111:2516-2520.2. Gore ME, Selby PJ, Viner C, et al. Intensive treat-ment of multiple myeloma and criteria for complete re -mission. Lancet. 1989;334:879-882.3. Anderson KC, Barut BA, Ritz J, et al. Autologousbone marrow transplantation therapy for multiple myelo-

ma. Eur J Haematol Suppl. 1989;51:157-163.4. Blank PR, Levin R, Pestalozzi BC, et al. Cost differences among treat-

ment options for patients with refractory myeloma previously treatedwith high-dose chemotherapy and autologous stem-cell transplanta-tion: an analysis from the U.S. and Swiss perspectives. J Clin Oncol.2011;29(suppl). Abstract e16569.

5. Wang S-T, Huang H, Ba-Mancini A, et al. The cost-effectiveness ofbortezomib plus melphalan and prednisone versus lenalidomide plusmelphalan and prednisone with continuous lenalidomide maintenancetreatment for the initial treatment of multiple myeloma in the UnitedStates. Blood (ASH Annual Meeting Abstracts). 2010;116. Abstract 2563.

6. Bensinger WI. Role of autologous and allogeneic stem cell transplanta-tion in myeloma. Leukemia. 2009;23:442-448.

7. Jagannath S, Barlogie B, Berenson J, et al. A phase 2 study of two dosesof bortezomib in relapsed or refractory myeloma. Br J Haematol. 2004;127:165-172.

8. Jagannath S, Barlogie B, Berenson JR, et al. Updated survival analysesafter prolonged follow-up of the phase 2, multicenter CREST study ofbortezomib in relapsed or refractory multiple myeloma. Br J Haematol.2008;143:537-540.

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11. Richardson PG, Sonneveld P, Schuster MW, et al. Safety and efficacyof bortezomib in high-risk and elderly patients with relapsed multiplemyeloma. Br J Haematol. 2007;137:429-435.

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13. Jagannath S, Richardson PG, Barlogie B, et al. Bortezomib in combina-tion with dexamethasone for the treatment of patients with relapsedand/or refractory multiple myeloma with less than optimal response tobortezomib alone. Haematologica. 2006;91:929-934.

14. San Miguel JF, Schlag R, Khuageva NK, et al. Bortezomib plus melpha-


Table 3. Risk Assessment for VTE Prophylaxis in Patients Treated with Immunomodulatory Agents45

Individual Risk Factors Treatment-Related Risk Factors

Obesity (BMI ≥30 kg/m2)

Previous venous thromboembolism

Central venous catheter or pacemaker

Chronic renal disease (CrCl <40 mL/min)

Diabetes

Medications (erythropoietin, estrogen)

Immobility

General surgery

Trauma (major or lower extremity)

Blood clotting disorders

Number of Risk Factors Prophylaxis

0-1 Aspirin 81-325 mg daily

2+ LMWH (enoxaparin 40 mg SC daily, or equivalent)

Warfarin (INR 2-3)

BMI indicates body mass index; CrCl, creatinine clearance; INR, international normalized ratio;LMWH, low-molecular-weight heparin; SC, subcutaneously; VTE, venous thromboembolism.

High-dose dexamethasone (≥480 mg/month or 120 mg/week)

Doxorubicin

Combination chemotherapy

lan and prednisone for initial treatment of multiple myeloma. N Engl JMed. 2008;359:906-917.

15. Velcade [package insert]. Cambridge, MA: Millennium Pharmaceu -ticals; December 2009.

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17. Menashe J. Managing and avoiding bortezomib toxicity. CommunityOncology. 2007;8:480-484.

18. Weycker D, Malin J, Edelsberg J, et al. Cost of neutropenic complica-tions of chemotherapy. Ann Oncol. 2008;19:454-460.

19. Badros A, Goloubeva O, Dalal JS, et al. Neurotoxicity of bortezomibtherapy in multiple myeloma: a single-center experience and review ofthe literature. Cancer. 2007;110:1042-1049.

20. Richardson PG, Xie W, Mitsiades C, et al. Single-agent bortezomib inpreviously untreated multiple myeloma: efficacy, characterization ofperipheral neuropathy, and molecular correlations with response andneuropathy. J Clin Oncol. 2009;27:3518-3525.

21. Dimopoulos MA, Mateos MV, Richardson PG, et al. Risk factors for,and reversibility of, peripheral neuropathy associated with bortezomib-melphalan-prednisone in newly diagnosed patients with multiplemyeloma: subanalysis of the phase 3 VISTA study. Eur J Haematol.2011;86:23-31.

22. Corso A, Mangiacavalli S, Varettoni M, et al. Bortezomib-inducedperipheral neuropathy in multiple myeloma: a comparison between pre-viously treated and untreated patients. Leuk Res. 2010;34:471-474.

23. Richardson PG, Laubach JP, Schlossman RL, et al. Complications ofmultiple myeloma therapy, part 1: risk reduction and management ofperipheral neuropathy and asthenia. J Natl Compr Cancer Netw. 2010;8(suppl 1):S4-S12.

24. Cata JP, Weng HR, Burton AW, et al. Quantitative sensory findings inpatients with bortezomib-induced pain. J Pain. 2007;8:296-306.

25. Cavaletti G, Gilardini A, Canta A, et al. Bortezomib-induced periph-eral neurotoxicity: a neurophysiological and pathological study in therat. Exp Neurol. 2007;204:317-325.

26. Richardson PG, Briemberg H, Jagannath S, et al. Frequency, character-istics, and reversibility of peripheral neuropathy during treatment ofadvanced multiple myeloma with bortezomib. J Clin Oncol. 2006;24:3113-3120.

27. Bringhen S, Larocca A, Rossi D, et al. Efficacy and safety of once-week-ly bortezomib in multiple myeloma patients. Blood. 2010;116:4745-4753.

28. Moreau P, Pylypenko H, Grosicki S, et al. Subcutaneous versus intra-venous administration of bortezomib in patients with relapsed multiplemyeloma: a randomised, phase 3, non-inferiority study. Lancet Oncol.2011;12:431-440.

29. Richardson PG, Sonneveld P, Schuster MW, et al. Reversibility ofsymptomatic peripheral neuropathy with bortezomib in the phase IIIAPEX trial in relapsed multiple myeloma: impact of a dose-modifica-tion guideline. Br J Haematol. 2009;144:895-903.

30. Delforge M, Bladé J, Dimopoulos MA, et al. Treatment-related periph-eral neuropathy in multiple myeloma: the challenge continues. LancetOncol. 2010;11:1086-1095.

31. Hausheer FH, Schilsky RL, Bain S, et al. Diagnosis, management, andevaluation of chemotherapy-induced peripheral neuropathy. SeminOncol. 2006;33:15-49.

32. Chanan-Khan A, Sonneveld P, Schuster MW, et al. Analysis of herpeszoster events among bortezomib-treated patients in the phase III APEXstudy. J Clin Oncol. 2008;26:4784-4790.

33. Vickrey E, Allen S, Mehta J, et al. Acyclovir to prevent reactivation ofvaricella zoster virus (herpes zoster) in multiple myeloma patientsreceiving bortezomib therapy. Cancer. 2009;115:229-232.

34. Johns Hopkins ABX Guide. www.hopkinsguides.com/hopkins/ub/view/Johns_Hopkins_ABX_Guide/540007/all/Acyclovir. Accessed August18, 2011.

35. Dimopoulos M, Spencer A, Attal M, et al. Lenalidomide plus dexa-methasone for relapsed or refractory multiple myeloma. N Engl J Med.2007;357:2123-2132.

36. Weber DM, Chen C, Niesvizky R, et al. Lenalidomide plus dexametha-sone for relapsed multiple myeloma in North America. N Engl J Med.2007;357:2133-2142.

37. Chen C, Reece DE, Siegel D, et al. Expanded safety experience withlenalidomide plus dexamethasone in relapsed or refractory multiplemyeloma. Br J Haematol. 2009;146:164-170.

38. Morgan GJ, Schey SA, Wu P, et al. Lenalidomide (Revlimid), in com-bination with cyclophosphamide and dexamethasone (RCD), is an

effective and tolerated regimen for myeloma patients. Br J Haematol.2007;137:268-269.

39. Baz R, Walker E, Karam MA, et al. Lenalidomide and pegylated liposo-mal doxorubicin-based chemotherapy for relapsed or refractory multiplemyeloma: safety and efficacy. Ann Oncol. 2006;17:1766-1771.

40. Knop S, Gerecke C, Liebisch P, et al. Lenalidomide, adriamycin, and dex-amethasone (RAD) in patients with relapsed and refractory multiplemyeloma: a report from the German Myeloma Study Group DSMM(Deutsche Studiengruppe Multiples Myelom). Blood. 2009;113:4137-4143.

41. Mateos MV. Management of treatment-related adverse events in pa tientswith multiple myeloma. Cancer Treat Rev. 2010;36(suppl 2):S24-S32.

42. Rajkumar SV, Jacobus S, Callander NS, et al. Lenalidomide plus high-dose dexamethasone versus lenalidomide plus low-dose dexamethasoneas initial therapy for newly diagnosed multiple myeloma: an open-labelrandomised controlled trial. Lancet Oncol. 2010;11:29-37.

43. Hirsh J. Risk of thrombosis with lenalidomide and its prevention withaspirin. Chest. 2007;131:275-277.

44. Revlimid [package insert]. Summit, NJ: Celgene Corporation; October2010.

45. Palumbo A, Rajkumar SV, Dimopoulos MA, et al. Prevention ofthalidomide- and lenalidomide-associated thrombosis in myeloma.Leukemia. 2008;22:414-423.

46. Cook R. Economic and clinical impact of multiple myeloma to man-aged care. J Manag Care Pharm. 2008;14(7 suppl):19-25.

47. Schiff D, Wen PY, van den Bent MJ. Neurological adverse effects causedby cytotoxic and targeted therapies. Nat Rev Clin Oncol. 2009;6:596-603.

48. Singhal S, Mehta J, Desikan R, et al. Antitumor activity of thalidomidein refractory multiple myeloma. N Engl J Med. 1999;341:1565-1571.

49. Glasmacher A, Hahn C, Hoffmann F, et al. A systematic review ofphase-II trials of thalidomide monotherapy in patients with relapsed orrefractory multiple myeloma. Br J Haematol. 2006;132:584-593.

50. von Lilienfeld-Toal M, Hahn-Ast C, Furkert K, et al. A systematicreview of phase II trials of thalidomide/dexamethasone combinationtherapy in patients with relapsed or refractory multiple myeloma. Eur JHaematol. 2008;81:247-252.

51. Rajkumar SV, Blood E, Vesole D, et al; Eastern Cooperative OncologyGroup. Phase III clinical trial of thalidomide plus dexamethasone com-pared with dexamethasone alone in newly diagnosed multiple myelo-ma: a clinical trial coordinated by the Eastern Cooperative OncologyGroup. J Clin Oncol. 2006;24:431-436.

52. Ludwig H, Hajek R, Tóthová E, et al. Thalidomide-dexamethasonecompared with melphalan-prednisolone in elderly patients with multi-ple myeloma. Blood. 2009;113:3435-3442.

53. Rajkumar SV, Rosiñol L, Hussein M, et al. Multicenter, randomized,double-blind, placebo-controlled study of thalidomide plus dexametha-sone compared with dexamethasone as initial therapy for newly diag-nosed multiple myeloma. J Clin Oncol. 2008;26:2171-2177.

54. Morgan GJ, Davies FE, Gregory WM, et al. Cyclophosphamide,thalidomide, and dexamethasone (CTD) as initial therapy for patientswith multiple myeloma unsuitable for autologous transplantation.Blood. 2011;118:1231-1238.

55. Lokhorst HM, van der Holt B, Zweegman S, et al. A randomized phase3 study on the effect of thalidomide combined with adriamycin, dexa -methasone, and high-dose melphalan, followed by thalidomide mainte-nance in patients with multiple myeloma. Blood. 2010;115:1113-1120.

56. Palumbo A, Bringhen S, Caravita T, et al. Oral melphalan and pred-nisone chemotherapy plus thalidomide compared with melphalan andprednisone alone in elderly patients with multiple myeloma: ran-domised controlled trial. Lancet. 2006;367:825-831.

57. Palumbo A, Bringhen S, Liberati AM, et al. Oral melphalan, prednisone,and thalidomide in elderly patients with multiple myeloma: updatedresults of a randomized controlled trial. Blood. 2008;112:3107-3114.

58. Hulin C, Facon T, Rodon P, et al. Efficacy of melphalan and prednisoneplus thalidomide in patients older than 75 years with newly diagnosedmultiple myeloma: IFM 01/01 trial. J Clin Oncol. 2009;27:3664-3670.

59. Facon T, Mary JY, Hulin C, et al. Melphalan and prednisone plus thali -domide versus melphalan and prednisone alone or reduced-intensityautologous stem cell transplantation in elderly patients with multiplemyeloma (IFM 99-06): a randomised trial. Lancet. 2007;370:1209-1218.

60. Zervas K, Dimopoulos MA, Hatzicharissi E, et al. Primary treatment ofmultiple myeloma with thalidomide, vincristine, liposomal doxorubicinand dexamethasone (T-VAD doxil): a phase II multicenter study. AnnOncol. 2004;15:134-138.

61. Thalomid [package insert]. Summit, NJ: Celgene Corporation; February2007.


62. Wulff CH, Høyer H, Asboe-Hansen G, et al. Development of polyneu-ropathy during thalidomide therapy. Eur J Haematol. 2008;81:247-252.

63. Tseng S, Pak G, Washenik K, et al. Rediscovering thalidomide: a reviewof its mechanism of action, side effects, and potential uses. J Am AcadDermatol. 1996;35:969-979.

64. van Marion AM, Auwerda JJ, Lisman T, et al. Prospective evaluation ofcoagulopathy in multiple myeloma patients before, during and after var-ious chemotherapeutic regimens. Leuk Res. 2008;32:1078-1084.

65. Zangari M, Anaissie E, Barlogie B, et al. Increased risk of deep-veinthrombosis in patients with multiple myeloma receiving thalidomideand chemotherapy. Blood. 2001;98:1614-1615.

66. Minnema MC, Breitkreutz I, Auwerda JJ, et al. Prevention of venousthromboembolism with low molecular-weight heparin in patients withmultiple myeloma treated with thalidomide and chemotherapy.Leukemia. 2004;18:2044-2046.

67. Zangari M, Barlogie B, Anaissie E, et al. Deep vein thrombosis in pa -tients with multiple myeloma treated with thalidomide and chemo -

therapy: effects of prophylactic and therapeutic anticoagulation. Br JHaematol. 2004;126:715-721.

68. Baz R, Li L, Kottke-Marchant K, et al. The role of aspirin in the pre-vention of thrombotic complications of thalidomide and anthracycline-based chemotherapy for multiple myeloma. Mayo Clin Proc. 2005;80:1568-1574.

69. Niesvizky R, Martínez-Baños D, Jalbrzikowski J, et al. Prophylactic low-dose aspirin is effective antithrombotic therapy for combination treat-ments of thalidomide or lenalidomide in myeloma. Leuk Lymphoma.2007;48:2330-2337.

70. Dunn CJ, Goa KL. Enoxaparin. A pharmacoeconomic appraisal of itsuse in thromboembolic prophylaxis after total hip arthroplasty.Pharmacoeconomics. 1996;10:179-190.

71. Ghobrial IM, Rajkumar SV. Management of thalidomide toxicity.J Support Oncol. 2003;1:194-205.

72. Palumbo A, Facon T, Sonneveld P, et al. Thalidomide for treatment ofmultiple myeloma: 10 years later. Blood. 2008;111:3968-3977.



PAYER PERSPECTIVE

Over the past decade, the use of bortezomib, lenalido-mide, and thalidomide, with or without autologousstem cell transplant, has significantly im proved out-

comes for patients with multiple myeloma (MM). Several of theregimens now listed as category 1 recommendations by theNational Comprehensive Cancer Network (NCCN) for thetreatment of MM include 1 or more of these agents.1 Category1 designation refers to uniform NCCN consensus that the inter-vention is appropriate based on high-level evidence. Individualstreated with new, more effective regimens are now survivingtwice as long as those treated only a decade ago with therapiessuch as melphalan plus prednisone.2

These advances are truly revolutionary, as it is rare to see theemergence of therapies that can cause such a paradigm shift inthe natural course of an incurable disease like MM. However,this excitement comes at a hefty price; namely, the direct andindirect costs associated with treatment. As a side note, thisdilemma is not relegated exclusively to myeloma. We are nowseeing new oncology therapies enter the market with a mini-mum of $100,000 per course of therapy, as evidenced by thetargeted agents ipilimumab, for the treatment of melanoma,and brentuximab, for the treatment of lymphoma.3,4 This risein the cost of therapy is not surprising; it was inevitable, as wehave witnessed in the treatment of other disease states such asmultiple sclerosis.5

The main article in this publication provides an excellentoverview of side effects associated with bortezomib, lena -lidomide, and thalidomide. I think it is important for clini-cians and payers to focus considerable attention on the pre-vention and management of myelosuppression and venousthromboembolism (VTE), as they represent 2 ends of thespectrum as it relates to overall costs associated with care.Myelosuppression as a complication of myeloma therapycannot be overlooked. Granulocyte colony-stimulating fac-tors are often required to manage this adverse event, andtheir use can significantly increase the overall cost of treat-ment. The addition of erythropoiesis-stimulating agents tolenalidomide-based therapy may also contribute greatly tothe cost of care. It is important for clinicians and payers tobe aware of the recommended guidelines pertaining to the

use of these products to prevent variability in utilization,which will inevitably result in additional costs that may nothave been considered previously.6

Thromboembolism, on the other hand, is readily preventa-ble with low-cost therapy. The cost of thromboprophylaxiswith agents such as aspirin, warfarin, or low-molecular-weightheparin is very reasonable when compared with the high costof treating deep vein thrombosis or pulmonary embolism oncethey occur. In addition, the incidence of VTE can often bereduced with lower doses of dexamethasone.7

In addition to side effect management, a key ingredient inproviding value-based care for patients diagnosed with canceris that of palliative care. This approach is aimed at improvingthe quality of life of patients and their families through preven-tion and relief of suffering by means of early identification,impeccable assessment, and tolerable treatment.8 For manypatients diagnosed with cancer, the primary focus is on the var-ious therapeutic options and the management of associatedtoxicities, while a discussion and plan involving palliative careis often overlooked. Palliative measures are most effectivewhen implemented early in the course of treatment, andshould be considered for every patient. Formulating a pallia-tive care plan, in addition to being aware of the potential sideeffects of therapy and providing appropriate preventive andmanagement strategies, are all critical to the overall success oftreating MM. ■

References1. National Comprehensive Cancer Network. NCCN Clinical Practice

Guidelines in Oncology: Multiple Myeloma. Version 1.2011, NCCN Website. www.nccn.org/professionals/physician_gls/pdf/myeloma.pdf. AccessedAugust 2011.

2. Kumar SK, Rajkumar SV, Dispenzieri A, et al. Improved survival in multi-ple myeloma and the impact of novel therapies. Blood.2008;111:2516-2520.

3. Murray L, ed. 2011 Red Book (Micromedex 2.0 Online). Montvale, NJ:Thompson PDR; 2011. Accessed May 25, 2011.

4. Seattle Genetics Sets Adcetris Price. BioCentury via BioPortfolio. www.bioportfolio.com/news/article/777951/Seattle-Genetics-Sets-Adcetris-Price.html. Accessed August 27, 2011.

5. von Schaper E, Kresge N. Novartis’ Gilenya spurs rivals to increase price.Bloomberg News. http://articles.sfgate.com/2011-03-23/business/29176786_1_tysabri-avonex-novartis-spokesman/2. Accessed August 26, 2011.

6. Wright JD, Neugut AI, Wilde ET, et al. Physician characteristics and vari-ability of erythropoiesis-stimulating agent use among Medicare patientswith cancer. J Clin Oncol. 2011;29(suppl). Abstract 6020.

7. Rajkumar SV, Jacobus S, Callander NS, et al. Lenalidomide plus high-dosedexamethasone versus lenalidomide plus low-dose dexamethasone as ini-tial therapy for newly diagnosed multiple myeloma: an open-label ran-domised controlled trial. Lancet Oncol. 2010;11:29-37.

8. World Health Organization. WHO Definition of Palliative Care. www.who.int/cancer/palliative/definition/en/. Accessed August 23, 2011.

Value-Based Approach to Managing Adverse Events in Myeloma

By Atheer A. Kaddis, PharmDVice President, Managed MarketsDiplomat Specialty Pharmacy, Flint, MI


Peripheral neuropathy (PN) is a potentially debilitatingcondition that can lead to significantly decreased qual-ity of life and the interruption of vital therapy. In

patients with multiple myeloma (MM), neuropathy may be acomplication of the disease itself, or it may be a side effectof specific therapies.1,2 Bortezomib and thalidomide—2 veryactive agents in myeloma—have both been associated withthe development of PN.2 Therefore, to ensure that patientsremain on therapy, it is extremely important to preventand/or minimize this painful symptom whenever possible.

Bortezomib-associated PN is well documented in MM butis generally reversible upon dose reduction or discontinua-tion.2,3 Recent studies evaluating a new administration routeand dosing schedule of this agent have shown a reduced inci-dence of neuropathy, resulting in increased tolerability anddecreased overall healthcare costs.

In a multicenter, randomized, phase 3 trial, Moreau andcolleagues compared the efficacy and safety of subcutaneous(SC) versus intravenous (IV) bortezomib at the standard 1.3-mg/m2 dose twice weekly in patients with previously treatedMM.4 The overall response rates were similar in both groupsof patients (42%). However, those in the SC group experi-enced significantly less overall PN than those in the IV group(38% vs 53%; P=.04).4 In addition, SC bortezomib does notappear to cause the hypotension that is sometimes associatedwith IV administration; therefore, fluid boluses may not benecessary when using the drug in this fashion. Thus, SCadministration may result in decreased monitoring time inthe infusion area and potentially less admissions for infusion-related reactions. Indeed, an exciting opportunity may evenexist for the administration of SC bortezomib at home,which would eliminate numerous infusion visits. It remainsto be seen if this option is feasible, but the safety profile of SCbortezomib suggests that it is a possibility.

Administering bortezomib once weekly instead of twiceweekly has also been shown to be of value in reducing theincidence of PN. In the phase 3 GIMEMA trial, Bringhenand colleagues compared once-weekly versus twice-weekly

bortezomib in transplant-ineligible MM patients and foundsimilar efficacy between groups, but with significantly de -creased rates of grade 3/4 PN in the once-weekly group (8%vs 28%; P <.001).5 Therefore, it appears that administeringbortezomib once weekly, in select patient populations, canproduce good responses while allowing for fewer clinic visits(and thus decreased costs) and a lower incidence of treat-ment-related toxicity.

Thalidomide-associated PN is a cumulative and dose-related toxicity in MM.2,6 Unfortunately, the neuropathycaused by this agent may be irreversible if not identified earlyand managed appropriately. Therefore, it is imperative toassess patients regularly for the development of thalidomide-associated neuropathy and to promptly decrease and/or dis-continue treatment when necessary, as discussed in the mainarticle of this publication.7,8

Pharmacists play a vital role in helping patients to receivethe greatest benefits from treatment. Assessing patients atevery visit for signs and symptoms of PN is critical, as thisallows for prompt dose modifications of bortezomib andthalidomide when necessary. Minimizing PN through the useof SC and once-weekly bortezomib offers a value-basedapproach to therapy. Strategies such as these can lead toincreased dose intensity overall and improved response totherapy, thus optimizing care for the patient with myeloma. ■

References1. Malhotra P, Choudhary PP, Lal V, et al. Prevalence of peripheral neu-

ropathy in multiple myeloma at initial diagnosis. Leuk Lymphoma. 2011Jul 13. [Epub ahead of print].

2. Delforge M, Bladé J, Dimopoulos MA, et al. Treatment-related periph-eral neuropathy in multiple myeloma: the challenge continues. LancetOncol. 2010;11:1086-1095.

3. Richardson PG, Xie W, Mitsiades C, et al. Single-agent bortezomib inpreviously untreated multiple myeloma: efficacy, characterization ofperipheral neuropathy, and molecular correlations with response andneuropathy. J Clin Oncol. 2009;27:3518-3525.

4. Moreau P, Pylypenko H, Grosicki S, et al. Subcutaneous versus intra-venous administration of bortezomib in patients with relapsed multiplemyeloma: a randomized, phase 3, non-inferiority study. Lancet Oncol.2011;12:431-440.

5. Bringhen S, Larocca A, Rossi D, et al. Efficacy and safety of once-weeklybortezomib in multiple myeloma patients. Blood. 2010;116:4745-4753.

6. Mateos MV. Management of treatment-related adverse events in pa tientswith multiple myeloma. Cancer Treat Rev. 2010;36(suppl 2):S24-S32.

7. Tariman JD, Love G, McCullagh E, et al. Peripheral neuropathy associ-ated with novel therapies in patients with multiple myeloma: consensusstatement of the IMF nurse leadership board. Clin J Oncol Nurs. 2008;12(3 suppl):29-36.

8. Thalidomide [package insert]. Summit, NJ: Celgene Corporation;February 2007.

By Stephanie S. Minich, PharmD, BCOPClinical Pharmacist, Hematology/OncologyClinical Assistant ProfessorUniversity of Michigan Health System, Ann Arbor, MI

Preventing and Treating Peripheral Neuropathy in Myeloma

PHARMACIST PERSPECTIVE


NOTES


AVBCC411

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About the Association for Value-Based Cancer CareAVBCC is the fastest growing national specialty organ-ization dedicated to improving the care of cancerpatients and their quality of life, by discussing, consider-ing, and evaluating the value equation as it relates tonew and existing cancer therapies. This organization,which currently consists of over 300 members, wasestablished to provide a network for payers and oncolo-gy healthcare professionals to interact and network inorder to promote optimal care for patients and theirfamilies.

____________________

MissionThe mission of AVBCC is to provide a forum for payers,providers, and the entire oncology team to consider andevaluate the cost-value issues particular to cancer treat-ments and its impact on patient care and outcomes. Thisunique focus is achieved through discussions and collab-orations with those involved in evaluating therapies,treating patients, and paying for care.

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VisionThe vision of AVBCC is to provide a unique forum forall stakeholders to discuss, consider, and evaluate thecost-value issues particular to new cancer therapies, as itrelates to all cancer patients so they may benefit withoptimal outcomes.

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Value-Based Care: In Multiple Myeloma

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