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

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

Why Transplant Early? It is the standardIt is the standard It is less toxic than alternativesIt is less toxic than alternatives It is curative therapyIt 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: ; Attal M, et al. N Engl J Med. 1996;335:91-97.

ASCT vs. Conventional CT Results of Randomized Studies Attal, et al. 1996IFM90 CT Auto Tx Fermand, et al. 2005MAG91 CT Auto Tx Child, et al. 2003MRC7 CT Auto Tx Palumbo, et al. 2004IMMSG CT Auto Tx Blade, et al. 2005PETHEMA CT Auto Tx Barlogie, Kyle, et al. 2006USIG CT Auto Tx a % at 7 years 17% % at 7 years 38%.03 <.001 Patients (n) OS (months) P Value EFS (months) CR (%) 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 a P =.07

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

Months HDT/PSCT: Upfront vs. Rescue Treatment Show Similar OS but Better QOL with Early SCT *Time without symptoms and treatment toxicity Fermand J, et al. Blood. 1998;92: P =.92 n=202

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

Why Transplant Early? It is the standardIt is the standard It induces more remissionsIt induces more remissions It is curative therapyIt is curative therapy

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

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

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

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 Tricot G. Blood 87;

Allo Tx Graft vs. MyelomaGraft vs. Myeloma Syngeneic TransplantSyngeneic Transplant

Trasplante Syngeneico Bashey et al, BBMT 20089

Allo Tx Graft vs. MyelomaGraft vs. Myeloma Syngeneic TransplantSyngeneic Transplant Myeloablative:Myeloablative: Less disease recurrence -AbandonedLess disease recurrence -Abandoned

Allo Tx Graft vs. MyelomaGraft vs. Myeloma Syngeneic TransplantSyngeneic Transplant MyeloablativeMyeloablative Non-MyeloablativeNon-Myeloablative

Bjorkstrand et al, JCO 29;22:

Allo-RIC vs. Auto StudyNEligib TX Cond GVH N Tx AgePFSSurv Hovon260HLA sib2 Gy TBI CSA-MMF 6y 6y 6y Gimema120HLA sib2Gy 4y 4y 4y y CTN700+HLA sib2GyTBI CSA-MMF 3y 3y 3y 3y EBMT- NMAM 375HLA-sibFlu 2 Gy TBI CSA-MMF 8y 8y IFM284*HLA SibBU 4 Flu ATG CSA-MTX 5y PETHE MA 110**HLA-sibFlu-Mel * Only B2M >3 and 13q del** no nCR after Tx1

Allo-RIC vs. Auto StudyNEligib TX Cond GVH N Tx AgePFSSurv Hovon260HLA sib2 Gy TBI CSA-MMF 6y 6y 6y Gimema120HLA sib2Gy 4y 4y 4y y CTN700+HLA sib2GyTBI CSA-MMF 3y 3y 3y 3y EBMT- NMAM 375HLA-sibFlu 2 Gy TBI CSA-MMF 8y 8y Blood , 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 Gimema Hovon CTN EBMT

EBMT: Myeloma with 13q

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

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

Graft vs. Myeloma Optimized? Tricot G. Blood 87; Lenalidomide? Pomalidomide? Vaccines?

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 YoF35 YoF MM del 17p, IgGMM del 17p, IgG 2012 Auto: PR2012 Auto: PR RelapseRelapse VDT-PACE: PRVDT-PACE: PR Haplo cord:Haplo cord:

Case 2 MM IgAMM IgA ETET ChloromaChloroma Cytarabine-Arac + BortezomibCytarabine-Arac + Bortezomib PRPR URD TransplantURD Transplant Tx in 1 st remission Nl cytogenetics

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