Dr. Alan Teh , 2012
Multiple Myeloma
Sarah Newbury, the first reported patient with multiple myeloma.
A) Bone destruction in the sternum. (B) The patient with fractured femurs and right humerus. (C) Bone destruction involving the femur.
Timeline depicting the history and treatment of multiple myeloma from 1844 to the present.
Kyle R A , Rajkumar S V Blood 2008;111:2962-2972
Myeloma is a blood cancerIncidence : 0.7M/0.5 F per
100,000 population (NCR, 2003)
Median age: 60 years1/10 as common as leukaemias
What Is Multiple Myeloma?
Causes
Is not known for sureDecline in the immune systemBiological factorsCertain occupationsExposure to certain chemicals Exposure to radiationVirus
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What Is Multiple Myeloma?Cancer of plasma cells.Plasma cells come from B lymphocytes, and
produce antibodies (immunoglobulins). Myeloma cells produce abnormal
immunoglobulins.– Overproduce monoclonal protein or paraprotein.– Ineffective immunoglobulins.– Leads to decreased bone marrow function. – Destruction of bone tissue.
Plasma Cell
Mechanism of diseasePlasma cell proliferation - > anemia, bone
marrow suppression, infection risk
Osteoclasts - > boney lesions, fractures, increased blood calcium
Paraprotein, hypercalcemia -> renal failure
Hypercalcemia – polyuria, thirst, drowsiness, coma
MM: Clinical PresentationsAnemia - 73 percentBone pain - 58 percentElevated creatinine - 48 percentFatigue/generalized weakness - 32 percentHypercalcemia- 28 percentWeight loss - 24 percent, one-half of whom
had lost ≥ 9 kgEarly stage - asymptomatic
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Common Sites for Bone InvolvementSkullSpine
ThoracicLumbarVertebrae
PelvisLong bones Spinal cord –
compression can occur
http://www.emedicine.com/Radio/topic460.htm#section~Introduction
Slowly evolving cancerMGUS
Monoclonal Gammopathy of Unknown Significance
Asymptomatic myeloma
Symptomatic myeloma
Risk of MGUS Myeloma
Risk groupRelative
RiskRisk @ 20
yrs
Lowest risk: 1. M protein < 1.5 g/dL2. IgG subtype3. Normal FLC ratio
1 5%
Any 1 factor abnormal 5.4 21%
Any 2 factors abnormal 10.1 37%
All 3 factors abnormal 20.8 58%
Rajkumar, V et al. Blood . 2005
When I told a friend that I have cancer, he replied "I thought you were an Aries?".
Symptomatic myeloma= CRABhyperCalcaemiaRenal insufficiencyAnaemiaBone lesions
DiagnosisParaprotein (M-protein)
serum protein electrophoresis24 hr urine protein electrophoresisserum Free light chain
Bone marrow biopsyplasma cellschromosome analysis: Karyotyping, FISH
ImagingX Rays, MRI, PET scan
SPEP: Normal
SPEP: M-protein, M-spike
Bone Marrow
Cytogenetics
FISH
Normal Skull Xray
Lytic Bone Lesion
MM: PET Scan
Staging for MMInternational staging system (ISS)
Stage I — B2M <3.5 mg/L and serum albumin ≥3.5 g/dL
Stage II — neither stage I nor stage IIIStage III — B2M ≥5.5 mg/L
Median overall survival for patients with ISS stages I, II, and III are 62, 44, and 29 months
Cytogenenetics, FISHHigh risk (median survival 25 months): Intermediate risk (median survival 42
months)Standard risk (median survival 50 months)
What's the difference between God and a doctorGod doesn't think he’s a doctor
Cancer cures smoking, eventually
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Previous Challenges in MM Treatment • Currently incurable in most patients.• Long-term complete responses are rare. • Median survival with standard therapy
about 3 years.• Autologous stem cell transplant may
prolong progression free survival, but it’s not curative.
• Treatment of relapse:– No standard therapy. – Existing options inadequate.
New treatment options needed.
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MM Treatment OptionsConventional chemotherapy:
Melphalan Doxorubicin Cyclophosphamide
• Radiation therapy
• Stem cell transplantation:
– Autologous– Allogenic
• Novel therapeutics: – Thalidomide – Lenalidomide – Bortezomib
Thalomid® Prescribing Information, Revlimid® Prescribing Information; Velcade® Prescribing Information
• Steroid therapy: – Dexamethasone – Prednisone
MM: Treatment DecisionsIndications for treatmentRisk stratification
- age- co-morbidities
Eligibility for stem cell transplantation
Smoldering (asymptomatic) myelomaDeferral of chemotherapy until progression to
symptomatic diseaseFollow these patients closely, every 3 to 4
months, with serum protein electrophoresis, complete blood count, serum creatinine, and serum calcium
Metastatic bone survey should be considered annually because asymptomatic bone lesions may develop
MM: Indications for TreatmentAnemia (hemoglobin <10 g/dL or 2 g/dL
below normal)Hypercalcemia (serum calcium >11.5 mg/dL)Renal insufficiency (serum creatinine>2
mg/dL)Lytic bone lesions or severe osteopeniaExtramedullary plasmacytoma
Current Frontline Options
Conventional chemotherapySurvival ≤ 3 yrs
TransplantationProlongs survival 4-5 yrs
Novel agents targeting stromal interactions and associated signaling pathways have superiority over conventional chemotherapy- increased % total responders- increased depth of response
Myeloma treatment optionsEra of Novel therapy as frontline >
Conventional chemotherapy
Autologous transplantation (high dose chemotherapy and stem cell rescue) still an option for younger patients
Current Frontline Options
Examples of current Novel agent combinations:
Thalidomide based : TD, CTD, MPT
Bortezomib (Velcade) based: Vdex, VMP, CVD, PAD, VRD
Lenalidomide (Revlimid) based: LenDex, Lendex
Younger patientsTimingUpfront after initial therapy with
novel agentsSalvage for relapseSingle vs Tandem (Double)Low TRM - <3%
Autologous transplantation
Autologous transplant - ineligible Age >70 yearsSignificant comorbities (organ
function)Poor performance status
Allogeneic transplantationGenerally not recommended (outside
of clinical trials)High incidence of GVHDHigh TRM (> 40%)
RadiotherapySurgeryBone care – bisphosphonatesTransfusionsGrowth factors Treatment and prevention of
infections Monitoring, management and
prevention of s/e
Other treatment / Supportive care
Myeloma survival by decade
Assessment of response
Impact of Novel Therapies on Survivorship Care
Unexpected new long-term complicationsSecond cancersLong-term maintenance for survivors:
quality of lifeFamily/social problemsFinancial/insurance concernsOther
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Optimizing Survival: Importance of Health MaintenanceMM patients are expected to live longerProper health maintenance contributes
toward longer survival and quality of life
RelapseBiochemical
- significant increase in M-proteinClinical
- CRAB criteriaImportance of monitoring and
follow-up
Hope New drugs on the horizonCarfilzomibPomalidomidePanobinostatVorinostatElotuzumabOld drugs with new useBendamustine
Be informedhttp://myeloma.orgGroup support
meetingssupport groups
http://malaysianmedicine.com – Myeloma Support Group
Support
Mobile app
Myeloma Info mobile applicationmobile browser:http://malaysianmedicine.com/myelomainfo
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