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Myeloma and Transplant

Myeloma and Transplant. 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. Tale of Two Cases. 56-year-old female with symptomatic myeloma Multiple lytic lesions

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Myeloma and Transplant

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  1. Myeloma and Transplant Sergio A Giralt, MD Chief, Adult Bone Marrow Transplant ServiceDivision of Hematologic OncologyDepartment of MedicineMemorial Sloan-Kettering Cancer CenterNew York, New York

  2. Tale of Two Cases • 56-year-old female with symptomatic myeloma • Multiple lytic lesions • M peak 2.5 gms/dl IgA lambda • Creatinine 1.5 mg/dL • Marrow plasmacytosis 50% • β2M 6 g/dL • Cytogenetics by FISH del 13 and 17p- • 56-year-old female with symptomatic myeloma • Multiple lytic lesions • M peak 2.5 gms IgA lambda • Creatinine 1.5 mg/dL • Marrow plasmacytosis 50% • β2M 2 gm/dL • Cytogenetics diploid

  3. Impact of Chromosomal Abnormalities on Survival Outcomes in MM ISS = International Staging System. Avet-Loiseau et al, 2009.

  4. Questions Is there a preferred induction therapy? • Thalidomide/dexamethasone • Lenalidomide/dexamethasone • Bortezomib/dexamethasone • Doublet vs Triplet vs Quadruplet (IMiD®/bortezomib/dexamethasone +/- alkylator) Is the consolidation therapy the same for both? • Auto vs allo vs late SCT Role of maintenance therapy • All patients – high risk-only non CR patients

  5. VTD vs TD Induction → ASCT: Efficacy *≥ nCR and ≥ VGPR by central assessment. Cavo M et al. Blood. 2009;114:Abstract 351.

  6. VTD vs TD Induction → ASCT: PFS in Poor-Prognosis Subgroups Cox Regression Analysis Cavo M et al. Blood. 2009;114:Abstract 351.

  7. Outcomes in pts Age <65After Len/Dex Induction LD = lenalidomide + high-dose dexamethasone Ld = lenalidomide + low-dose dexamethasone Siegel D et al. Proc ASH 2010;Abstract 38.

  8. Is It Time For A New Early-vs-Late SCT Study? Optimal induction regimen COLLECT HD THERAPY + SCT A A A Maintenance A A A m m HARVEST AND HOLD SCT UPON RELAPSE m Risk profile

  9. Melphalan/Prednisone/Lenalidomide (MPR) vs MEL200/ASCT Following Lenalidomide/Dexamethasone (Ld) Induction Consolidation n=402 <65 years R A N D O M I Z E R A N D O M I Z E MPR (n=202) Melphalan: 0.18 mg/kg/d, days 1–4 Prednisone: 2 mg/kg/d, days 1–4 Lenalidomide: 10 mg/d, days 1–21 q 28 days ×6 No maintenance Lenalidomide: 25 mg, days 1–21 Low-dose Dex: 40 mg, days 1, 8, 15, 22 q 28 days ×4 Tandem MEL200 ASCT stem cells mobilized with cyclophosphamide + G-CSF Maintenance lenalidomide: 10 mg/d,Days 1–21 q 28 days until relapse Primary end point: PFS Palumbo A et al. Blood. 2009;114:Abstract 350.

  10. Tale of Two CasesHigh Risk • 56-year-old female with symptomatic myeloma • Multiple lytic lesions • M peak 2.5 gms IgA-lambda • Creatinine 1.5 mg/dL • Marrow plasmacytosis 50% • β2M 6 g/dL • Cytogenetics by FISH del 13 and 17p- • After 4 cycles of induction and autologous SCT consolidation paraprotein peak is still 0.1 gms/dl • She has an HLA identical donor • You would now recommend • 1) Allo SCT • 2) 2nd Autograft • 3) Maintenance lenalidomide • 4) Observation • 5) Maintenance thalidomide

  11. Tale of Two CasesStandard Risk • 56-year-old female with symptomatic myeloma • Multiple lytic lesions • M peak 2.5 gms IgA lambda • Creatinine 1.5 mg/dL • Marrow plasmacytosis 50% • β2M 2 gm/dL • Cytogenetics diploid • After 4 cycles of induction and autologous SCT consolidation paraprotein peak is 0 gms/dl. IFE is negative • She has an HLA identical donor • You would now recommend • 1) Allo SCT • 2) 2nd Autograft • 3) Maintenance lenalidomide • 4) Observation • 5) Maintenance thalidomide

  12. Tandem AutHCT with or without Maintenance Therapy (auto-auto) versus Single AuHCT Followed by HLA Matched Sibling Non-Myeloablative Allogeneic HCT (auto-allo) for Patients with Standard Risk Multiple Myeloma: Results from the BMT-CTN 0102 Trial Amrita Krishnan, Marcelo Pasquini, Marian Ewell, Edward A. Stadtmauer, Edwin Alyea III, Joseph Antin, Raymond Comenzo, Stacey Goodman, Parameswaran Hari, Robert Negrin, Muzaffar Qazilbash, Scott Rowley, Firoozeh Sahebi, George Somlo, David Vesole, Dan Vogl, Daniel Weisdorf, Nancy Geller, Mary M. Horowitz, Sergio Giralt, David Maloney On behalf of the Blood and Marrow Transplant Clinical Trials Network

  13. 1st Autologous Transplant N = 710 No Sibling Donor Auto-Auto N = 484 Sibling Donor Auto-Allo N = 226 Standard Risk N = 436 Standard Risk N = 189 High Risk N = 37 High Risk N = 48 Main groups compared

  14. 100 100 90 90 80 80 70 70 60 60 50 50 40 40 30 30 20 20 10 10 0 0 Survival Outcomes after the First Transplant: Auto-Auto vs. Auto-Allo: Intent-to-Treat Analysis Progression-Free Survival Overall Survival Auto/Auto, 80% @ 3yr Auto/Auto, 46% @ 3yr Auto/Allo, 77% @ 3yr Probability, % Auto/Allo, 43% @ 3yr p-value = 0.67 p-value = 0.19 Months 0 6 12 18 24 30 36 42 48 # at risk:Auto/Auto 436 395 348 292 242 213 178 54 42Auto/Allo 189 165 138 117 105 89 71 23 16 0 6 12 18 24 30 36 42 48 436 424 406 395 370 348 305 107 79189 183 167 160 156 143 124 43 27 With permission from Krishnan A et al. Proc ASH 2010;Abstract 41.

  15. 100 90 80 70 60 50 40 30 20 10 0 Cumulative Incidence of Chronic GVHD after Allogeneic Transplant Chronic GVHD @1 year 47% (95% CI: 39.2%, 55.6%) Chronic GVHD @ 2 years 54% (95% CI: 46.0%, 62.8%) Incidence, % 0 6 12 18 24 30 36 42 48 Months * Chronic GVHD treated as time-dependent covariate and adjusted for disease status at transplant. With permission from Krishnan A et al. Proc ASH 2010;Abstract 41.

  16. CTN Studies for Myeloma: STaMINA Trial • Age <70 • At least 3 months of systemic therapy • 3–9 months from start of therapy • Autologous PBSC graft of > 4 × 106 CD34 cells/kg Melphalan 200 mg/m2 Auto HCT Maintenance Lenalidomide × 3 yrs Melphalan 200 mg/m2 Auto HCT Maintenance Lenalidomide × 3 yrs Randomize Principal investigators:A. Krishnan G. Somlo E. Stadtmauer Bortezomib/Dex/Lenalidomide × 4 cycles Maintenance Lenalidomide × 3 yrs

  17. Summary • Who should be considered for autologous stem cell transplant? • All patients with symptomatic myeloma except: the frail, those unable or unwilling to do so. • How should a patient be transplanted? • Preferably on a clinical trial. Off protocol probably bortezomib induction (double vs triple based on risk category) for 2-4 cycles. Stem cell collection followed by mel 200 mg/m2 followed by maintenance lenalidomide if not in CR. • When should they be transplanted? • As part of initial therapy preferably, although salvage SCT is being more extensively explored. • With what should they be transplanted? • Autologous stem cells, although the role of allografting as upfront therapy should continue to be explored in young high risk patients.

  18. What is your preferred induction regimen for a younger transplant-eligible patient with multiple myeloma (MM)?

  19. Should post-transplant lenalidomide maintenance be used?

  20. What Clinicians Want to KnowA Live CME Event Addressing the Most Common Questions and Controversies in the Current Clinical Management of Select Hematologic CancersSunday, June 5, 20117:00 PM – 9:30 PMChicago, Illinois Moderator Neil Love, MD Faculty Sergio Giralt, MDJohn P Leonard, MD Lauren C Pinter-Brown, MD Antonio Palumbo, MDSusan M O’Brien, MDProfessor Michael Hallek

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