1 / 25

Future directions: Can we improve outcomes in relapsed/refractory DLBCL or aggressive NHL?

Future directions: Can we improve outcomes in relapsed/refractory DLBCL or aggressive NHL?. Bertrand Coiffier. Equipe « Pathologie des Cellules Lymphoïdes » UMR 5239 CNRS – UCB – ENS - HCL. The Lymphoma Study Association. Service d ’ Hématologie Hospices Civils de Lyon.

xue
Download Presentation

Future directions: Can we improve outcomes in relapsed/refractory DLBCL or aggressive NHL?

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Future directions: Can we improve outcomes in relapsed/refractory DLBCL or aggressive NHL? Bertrand Coiffier Equipe « Pathologie des Cellules Lymphoïdes » UMR 5239 CNRS – UCB – ENS - HCL The Lymphoma Study Association Service d’Hématologie Hospices Civils de Lyon

  2. One question, lot of possibilities • Outcome different according to settings, so treatment objectives are different • Relapse or refractory • First or later progression • Young or old • When is it palliative treatment? • When the objective is CR?

  3. Refractory patients • Patients who progress during chemotherapy (first line or later) • Patients who progress a few months after responding to chemotherapy • 6, 9, or 12 months? • Always associated with poor outcome • But not true for 20% to 30% of the “refractory” patients

  4. Studies with/without rituximab With rituximab Without rituximab

  5. Effect of modifying the threshold between early and late relapse 12 m 9 m 15 m

  6. Same observation in Italy - 2543 patients - All subtypes of lymphoma - 46% DLBCL Tarella et al. ASH 2012 Abst. 305

  7. PFS according to major prognosticfactors 64% N=160 Time fromprimarydiagnosis to failure Rituximab use at first line N=228 31% 62% N=147 N=241 30% Gisselbrecht C et al. JCO 2010;28:4184-4190

  8. GAUGUIN aNHL Phase II: End-of-treatment response in rituximab-refractory patients 63% of patients were previously refractory to a rituximab-containing regimen 100 CRCRuPR 80 60 Patients (%) 40 25% 16% 20 8% 0 All 400/400 mg 1,600/800 mg Rituximab refractory defined as patients who had a response of < 6 months or who failed to respond to a rituximab-containing regimen (rituximab monotherapy or in combination with chemotherapy)

  9. Results of a pivotal phase II study of brentuximab vedotin for patients with relapsed or refractory Hodgkin’s lymphoma A Younes et al. JCO 2012;30:2183

  10. IRC Responses by Type of Prior Therapy Other *denileukin diftitox, interferon.

  11. Relapsed patients • Patients who responded to prior line of therapy (CR or PR) • Some can be salvaged in 2nd line • 45-50% in young patients1 • Around 20% 2-year OS in elderly patients • No good data for 3rd line 1Gisselbrecht et al. JCO 2012

  12. 98-5 study: OS of relapsing patients Median: 6 months 5-y OS: 15 & 20%

  13. First take home message • Poor survival after progression in DLBCL • However, 20% to 50% of the patients can be salvage, depending on age • Even in primary refractory patients • Except for unfit patients, a second line therapy is mandatory • With the objective of cure or long term survival

  14. Which therapy (young patients)? • Objective in first progression: CR before transplant • CORAL: R-DHAP seems a little better than ICE • Other regimens? RIT? • No proven benefit of maintenance/consolidation • Other progressions: try allogeneic transplant if good response to salvage

  15. Which therapy (older patients)? • Older = Not fit for transplant • A few regimens: R-GemOx • Phases II of #50 patients • ORR 60%-80% • CR 30%-40% • Median PFS #9 months • Median OS # 12-18 months • Rituximab improves response

  16. Blood 2008;111:537 225 patients

  17. R-GemOx 46 patients ORR 83% CR 50%

  18. R-GemOx Phase II from GELA 48 DLBCL patients, ORR 60%, CR 44% PFS OS

  19. Eur J Haematol 2008;80:127 32 patients, ORR 43%, CR 34%

  20. Other regimens • Numerous new “targeted” drugs in phase II

  21. Other multidrug regimens • Lenalidomide & rituximab1 • Bendamustine & rituximab2 • ADC & rituximab3 • … • Usually no efficacy in refractory patients 1Zinzani et al. Clin Lymph MyelLeuk 2011;11:462; 2 Horn et al. Ann Hematol 2012;91:1579; 3Fayad et al. J ClinOncol 2013;on line

  22. Regimens for refractory patients • No studies directed specifically these patients, • particularly in first line • Even if it is the big challenge in DLBCL • Always mixed with relapsed patients • Rending interpretation very difficult

  23. Conclusion for relapsed patients • Incidence decreases with new regimens • Try to cure young ones at time of relapse with salvage and autotransplant • Not really a place for allogeneic transplant in first relapse • Best regimen for salvage to be defined • R-CT + new agent(s) • No demonstrated role for maintenance

  24. Conclusion for refractory patients • In first line, try to recognize them early on • Same problem for truly refractory or early progression • Design specific studies addressing this problem • Introduce new agents

More Related