Optimal Use of Transplant for Myeloma EarlyLatenonablative Koen

Optimal Use of Transplant for Myeloma Early-Late-nonablative Koen van Besien, MD, Ph. D Weill Cornell Medical College

Optimal Use of Transplant for Myeloma Transplant Early! Consider Allogeneic Transplant! Koen van Besien, MD, Ph. D Weill Cornell Medical College

Why Transplant Early? • It is the standard • It is less toxic than alternatives • It is curative therapy

High-Dose Therapy and Autologous SCT Improves PFS and OS in Younger Patients Child JA, et al. N Engl J Med. 2003; 348: 1875 -1883. ; Attal M, et al. N Engl J Med. 1996; 335: 91 -97.

ASCT vs. Conventional CT Results of Randomized Studies Attal, et al. 1996 Fermand, et al. 2005 Child, et al. 2003 Palumbo, et al. 2004 Blade, et al. 2005 Barlogie, Kyle, et al. 2006 IFM 90 MAG 91 MRC 7 IMMSG PETHEMA USIG CT Auto Tx CT Auto Tx Patients (n) CR (%) EFS OS (months) 100 5 18 44 100 22 27 57 96 20 19 48 94 36 25 a 48 200 9 20 42. 3 201 44 32 54. 1 98 6 16 43 97 25 28 58+ 83 11 33 66 81 30 42 61 255 11 261 11 16% at 7 years 17% 38% at 7 years 38% P Value. 03 <. 001 a. P =. 07 CT = chemotherapy; Auto Tx = autologous therapy; IFM = Intergroupe Francais du Myelome; IMMSG = Italian Multiple Myeloma Study Group; MAG = Group Myelome Autographe; MRC = Medical Research Council; USIG = US Intergroup

Why Transplant Early? • It is the standard. • It is less toxic than alternatives • It is curative therapy

HDT/PSCT: Upfront vs. Rescue Treatment Show Similar OS but Better QOL with Early SCT P =. 92 Months 64. 6 64. 0 39. 0 27. 8 22. 3 13. 0 n=202 *Time without symptoms and treatment toxicity Fermand J, et al. Blood. 1998; 92: 3131 -3136

Impact of ASCT on QOL of FL patients Andresen et al Leuk & Lymph, 2012; 53: 386 14

Why Transplant Early? • It is the standard • It induces more remissions • It is curative therapy

CR vs. n. CR/VGPR/PR vs. Menos Martinez-Lopez et al Blood. 2011; 118(3): 529 -534

Abstract Martinez-Lopez et al Blood. 2011; 118(3): 529 -534

Why Transplant Early? • It is the standard • It is less toxic than alternatives • Delaying curative therapy until after disease recurrence may result in loss of curability

Tricot G. Blood 87; 3 1996 1196 -1198. • Refractory Myeloma • Transient antitumor effect CTX, then TBI, thiotepa with T-cell depleted allograft • Progressive disease was documented before day 70 • 2 nd DLI resulted in complete disappearance of any disease • GVHD developed revealing a GVM effect

Allo Tx • Graft vs. Myeloma • Syngeneic Transplant

Trasplante Syngeneico Bashey et al, BBMT 20089

Allo Tx • Graft vs. Myeloma • Syngeneic Transplant • Myeloablative: • Less disease recurrence -Abandoned

Allo Tx • • Graft vs. Myeloma Syngeneic Transplant Myeloablative Non-Myeloablative

Fludarabine 30 mg/m 2, 2 Gy TBI, MMF, CSA DLI 3 months PR Bjorkstrand et al, JCO 29; 22: 3016 -3022

Allo-RIC vs. Auto Study N Eligib TX Hovon 260 Cond GVH N Tx Age PFS Surv HLA sib 2 Gy TBI CSA-MMF 99 54 28%@ 6 y 22%@ 6 y 55%@ 6 y Gimema 120 HLA sib 2 Gy TBI 60 50@ 4 y 25@ 4 y 60@ 4 y 45@4 y CTN 700+ HLA sib 2 Gy. TBI CSA-MMF 156 43@ 3 y 46 @ 3 y 77@ 3 y 80@ 3 y EBMTNMAM 375 HLA-sib Flu 2 Gy TBI 109 CSA-MMF 22 @8 y 12@8 y 49@ 8 y 36@ 8 y IFM 284* HLA Sib BU 4 Flu ATG CSA-MTX 65 54 19@5 y 22@5 y 40@ 5 y 45@5 y PETHE MA 110** HLA-sib Flu-Mel 140 25 52 60%@5 y 25%@5 y 60%@5 y * Only B 2 M >3 and 13 q del ** no n. CR after Tx 1

Allo-RIC vs. Auto Study N Eligib TX Hovon 260 Cond GVH N Tx Age PFS Surv HLA sib 2 Gy TBI CSA-MMF 99 54 28%@ 6 y 22%@ 6 y 55%@ 6 y Gimema 120 HLA sib 2 Gy TBI 60 50@ 4 y 25@ 4 y 60@ 4 y 45@4 y CTN 700+ HLA sib 2 Gy. TBI CSA-MMF 156 43@ 3 y 46 @ 3 y 77@ 3 y 80@ 3 y EBMTNMAM 375 HLA-sib Flu 2 Gy TBI 109 CSA-MMF 22 @8 y 12@8 y 49@ 8 y 36@ 8 y Blood 2012 119, 6219 Blood 2011, ; 117, 6721 Lancet Oncol 2011, 12, 1195 Blood 2013, 121, 5055

Auto-RIC vs. Auto: Relapse Hovon Gimema EBMT

Auto RIC vs. Auto: Survival Hovon Gimema CTN EBMT

EBMT: Myeloma with 13 q

PETHEMA: PFS After Allo vs. 2 nd Auto in <n. CR Rossinol Blood 2008

OS from the time of first relapse/progression in patients with multiple myeloma treated with auto/RICallo or auto alone. Survival after relapse is Superior in patients undergoing Allogeneic Transplant Gahrton G et al. Blood 2013; 121: 5055 -5063 © 2013 by American Society of Hematology

Graft vs. Myeloma Optimized? Lenalidomide? Pomalidomide? Vaccines? Tricot G. Blood 87; 3 1996 1196 -1198.

Conclusions • Toxicity of allogeneic Transplant has been reduced in recent years • With prolonged follow-up the benefit of allo transplant becomes more apparent. • Allogeneic Transplant is particularly attractive for poor prognosis patients. • The future: • Alternative donors • Avoidance of chronic GVHD • Early Allogeneic Transplant • Incorporation of Maintenance Strategies

Case 1 • • • 35 Yo. F MM del 17 p, Ig. G 2012 Auto: PR Relapse VDT-PACE: PR Haplo cord:

Case 2 Tx in 1 st remission Nl cytogenetics • • MM Ig. A ET Chloroma Cytarabine-Arac + Bortezomib • PR • URD Transplant

Conclusions • Autologous transplant remains the standard treatment for myeloma • It is well tolerated and may lead to superior QOL • Cure may be possible in a fraction of patients • Allogeneic transplantation should be considered, particularly in patients with adverse prognosis