Is there a role of HDT ASCT as consolidation therapy for first relapse follicular lymphoma in the post Rituximab era? Yes Bertrand Coiffier Service d Hématologie Hospices Civils de Lyon Equipe «Pathologie des Cellules Lymphoïdes» UMR 5239 CNRS UCB ENS - HCL The Lymphoma Study Association
Treatment of first relapse Patient status Age Performance status Co morbidities Characteristics of relapse On/off therapy Transformation Aggressiveness IPI Initial therapy Components Maintenance Duration of response Toxicities Patient wishes
Treatment of first relapse Objectives To obtain the longest survival To reach the longest PFS Try to have a 2 nd CR To obtain the best quality of life Use less toxic regimens even if less CRs Obtain a new CR with long PFS Try not to use agents with toxicity 3
Therapeutic strategy in FL Two philosophies Avoid chemotherapy as long as possible rituximab rituximab Tositumomab 90Y Ibritumomab other biologics combinations chemotherapy 0 2 3.5 4.5 5.5 7 y Try to reach a CR and have a long duration of CR R CHOP salvage R chemo + autologous transplant biologics 0 6 8 12 15 y 4
Autologous transplant in first relapse The standard of care for DLBCL No standard at all for follicular lymphoma However, why not use high dose therapy with autotransplant (HDT)?
CUP Trial for Follicular Lymphoma 1.0 Progression-Free Survival 0.8 Chemotherapy Unpurged Purged Events 20 9 11 Total 24 22 24 Probability 0.6 0.4 0.2 0 Patients at: Chemotherapy Unpurged Purged 0 12 24 36 48 60 72 84 Months 24 9 6 6 4 2 1 1 22 16 11 11 11 9 8 2 24 16 12 12 12 8 6 3 Schouten HC et al. J Clin Oncol. 2003;21:3918-3927
Autologous transplant in FL 324 FL patients transplanted in Lyon Overall survival of FL patients from date of HDT according to line Overall survival of FL patients from diagnosis according to line E Bachy et al. Best Pract Res Clin Haematol 2011;24:257
Autologous SCT Using Cyclophosphamide and Total Body Irradiation in Follicular Lymphoma 1.00 Overall Survival by Remission Number Probability 0.75 0.50 0.25 0.00 2nd Remission P<0.005 >3rd Remission 0 2 4 6 8 10 12 14 16 18 20 Years Barts and DFCI (unpublished data)
Why not do HDT in first relapse? Better to keep it for later Standard chemotherapy of immunotherapy do the same Not demonstrated as standard regimen Do not cure FL patients Too toxic
LYSA (GELA) experience No randomized study in relapsing patients Two studies looking at outcome of relapsing patients included in prospective randomized study for 1 st line treatment GELF 86 FL2000 Both showed a benefit of HDT and autotransplant
High dose Therapy with ASCT the best option in pts failing 1 st therapy Event free survival after relapse/pd Survival after relapse/pd Sebban, JCO 2008
Survival after Relapse or PD in FL patients failing primary therapy Sebban, JCO 2008
FL2000 ASCT at time of failure after R CHVP I in patients < 70 years Event free survival Overall survival ASCT N=13 ASCT N=13 No ASCT n=50 No ASCT n=50 Le Gouill et al., Hematologica 2011;96:1128
HDT in relapsing patients 100 consecutive patients in Calgary 25 refractory, 29 in >1 st relapse, and 24 in transformation AC Peters et al. Leuk Lymph 2011;52:2124
HDT in relapsing patients 100 consecutive patients in Calgary 25 refractory, 29 in >1 st relapse, and 24 in transformation AC Peters et al. Leuk Lymph 2011;52:2124
Patients not adequate for HDT Patients not treated with R CHOP Elderly patients (over 65?) Patients with other severe concomitant disease
Patients recommended for HDT Early progression after R CHOP PD during maintenance therapy PD after PR with R CHOP PD with high tumor burden PD with transformation
The Role of Autologous and Allogeneic Transplantation for Follicular Lymphoma I favor using autologous transplantation for patients with high risk disease who have early relapse following conventional therapy Low NRM (<5%) Risk of MDS/AML with TBI regimens May provide long term disease free survival Conditioning regimens including immunotherapy (radioimmunotherapy or Rituximab) promising Nonmyeloablative allogeneic transplantation provides a potentially curative therapy NRM is significant (15 25%) May provide salvage even following failed autologous transplant D Maloney 4 th Eur Cong Hematol Malignancies
Conclusions Not a treatment for all patients Good indication PR or SD after R CHOP Early relapses after R CHOP Transformation New drugs after failure of HDT or in patients not fit for HDT