Multiple myeloma

Myeloma 2013-What we know-What we don’t know and what we don’t know we don’t know Sergio A Giralt, MD Chief, Adult Bone Marrow Transplant Service Division of Hematologic Oncology Department of Medicine Memorial Sloan-Kettering Cancer Center New York, New York Disclosures • Grant Support – Celgene – Millenium – Onyx • Honoraria – – – – – Celgene Millenium Onyx Novartis Sanofi/Genzyme • Most important I am a transplanter Initial Presentation • • • • 45-year-old woman Presents with proteinuria Normal Physical Laboratory findings – Hemoglobin 11 gm/dl normal iron stores – Total proteinuria 5.82 g/day – Bence Jones protein (BJP) 3.6 g/day – Hypogammaglobulinemia – Albumin 3.9 g/dL – β2-microglobulin 4.7 mg/L – Creatinine 1.7 mg/dl – No paraprotein peak but kappa light chain 120000 with lambda light chain at 0.01 – Kappa/lambda ratio=12000000 • • • • • • Bone marrow biopsy – Cellularity 80% with 25% plasma cells – Cytogenetics 46, XX, inversion (p11;q13) FISH no abnormalities Skeletal survey: extensive lytic bone disease with healing fractures of left 7th and the 8th ribs MRI of the spine: diffuse hyper-intense homogenous signal on STIR sequence MRI of the pelvis: diffuse marrow infiltrative changes due to myeloma Comorbidities: Diabetic on metformin, no history of coronary artery disease or other comorbidities Multiple Myeloma: Analysis t(11;14) M0 M1 M2 M3 M4 M5 M6 M7 t(4:14) t(14;16) SC Pre Pro Early Mid SHM Myeloma PC t(6:14) Hyperdiploidy decades Images courtesy of Raphael Fonseca, MD ICS Multiple Myeloma Treatment Linesa Front-line treatment Consolidation Induction IMID:Thal-Len Proteosome Inhibitor: Bor-Car Steroids: Dex-Pred Alkylator: Cyclo-Mel Anthracycline: LipoDnr-Adr SCT Maintenance Relapsed Maintenance Observation IMID:Thal-Len Proteosome Inh-Bor Steroids:Dex-Pred Rescue IMID:Thal-Len-Pom Proteosome Inh:Bor-Car Steroids: Dex-Pred Alkylators:Mel-Cy-Benda Investigational Transplant eligible patients Bor/Dex = bortezomib, dexamethasone; Bor/Dex/Dox = bortezomib, dexamethasone, doxorubicin; Bor/Thal/Dex = bortezomib, thalidomide, dexamethasone; Len/Dex = lenalidomide, dexamethasone; SCT = stem-cell transplant; Thal/pred = thalidomide, prednsione; Bor/Liposomal/Dox = bortezomib, liposomal doxorubicin NCCN, 2009 a What we know… IS THERE AN OPTIMAL  INDUCTION REGIMEN? Protocol GIMEMA 26866138-MMY-3006 VTD vs TD incorporated into double ASCT for MM RANDOMIZATION INDUCTION • VEL-THAL-DEX INDUCTION • THAL-DEX PBSC COLLECTION • CTX TRANSPLANTATION • MEL 200 • MEL 200 CONSOLIDATION • VEL-THAL-DEX CONSOLIDATION • THAL-DEX MAINTENANCE • DEX RESPONSE TO PRIMARY THERAPY % of patients VTD (n=129) TD (n=127) P value CR+nCR 36