1. DLBCL with less than PR to second line therapy… Correcting a Misconception…. Koen van Besien, MD Weill Cornell Medical College, NY

2. TRMCCRCRPRNR Sensitive Relapse 441019 23 Relapse –PD at TX 2241035 Never in CR-PD at TX 34791510 High Dose Chemotherapy not all that useful for patients with progressive disease…

3. Relapsed Chemosensitive High-Dose Chemotherapy With ABMT Is Effective in Relapsed Chemosensitive DLBCL: Parma Study 215 patients treated with 2 cycles of DHAP 109 patients showed CR or PR and were randomized to – Conventional treatment: 4 more cycles of DHAP (n = 54) – High-dose treatment: BEAC (carmustine, etoposide, cytarabine, cyclophosphamide, and mesna) + ABMT (n = 55) Philip T, et al. N Engl J Med. 1995;333:1540–1545. 100806040200 0 15 30 45 60 75 90 Transplantation Conventional treatment P = 0.038 Transplantation (n = 49) Conventional treatment (n = 54) P = 0.001 Months after randomization 100806040200 0 15 30 45 60 75 90 Event-free survival Overall survival Survival (%)

4. Misconception…. High dose chemotherapy is not effective in those with progressive disease (NEJM 1987)  Limit studies to those with CR/PR to salvage (PARMA)  It does not work in those excluded from PARMA study  They should be offered investigational therapies (drugs or medical procedures that are under investigation in clinical trials regarding their safety and efficacy)

5. What are the Data?

6. Two studies… CIBMTR Vose et al, J Clin Oncol 19: 406-413, 2001 MDACC Popat et al, J Clin Oncol 16: 63-69, 1998

7. Outcome Of Autologous Transplant In Patients Never Achieving Remission CIBMTR Vose et al, J Clin Oncol 19: 406-413, 2001

8. Outcome of autologous transplant relates to remission status Popat et al, J Clin Oncol 16: 63-69, 1998

9. Can we identify predictors??? Vose et al, J Clin Oncol 19: 406-413, 2001 There is a cure rate for pts never achieving remission # prior therapies KS Age Role of prior XRT

10. Outcome of autologous transplant relates to remission status Popat et al, J Clin Oncol 16: 63-69, 1998

11. Is Allogeneic Transplant Preferable? Pro GVL effects… Tumor Free Grafts Everybody has a donor… Age limit’s don’t apply

12. Probability Of Relapse After Syngeneic Transplantation PROBABILITY, % YEARS ASC01_9.ppt Allo T-deplete Auto unpurged Allo T-replete 0 20 40 60 80 100 012354 Auto purged Syngeneic P < 0.01 89 patients syngeneic transplant. 30 intermediate grade lymphoma Bierman et al, J Clin Oncol 21, 3744, 2003

13. Allogeneic after Failure of Autologous in DLBCL Kim et al, Ann Hematol. 2014 Aug;93(8):1345-51.Ann Hematol. Rigacci et al, Ann Hematol. 2012 Jun;91(6):931-9Ann Hematol.

14. Everybody has a donor…. Survival in Patients over age 50 URD vs. HC

15. Haplo Cord for Lymphoma 22 Age54 (24-72) Diagnosis HL5 CLL5 (1 Richter) MCL3 (2 Blastoid) DLBCL (MYC)2 FL Transformed1 MF2 PTCL4 (ALCL, AngImm, HS) Chemo Response Refractory (less than PR) 11 Chemo Sensitive11 MFU Survivors: 11 months (2-71)

16. Is Allogeneic Transplant Preferable? Pro GVL effects… Tumor Free Grafts Everybody has a donor… Age limit’s don’t apply Con Still a much more complex procedure The same prognostic factors apply…

17. Role of PET scanning after allogeneic SCT for NHL Kenkre et al, Leukemia and Lymphoma, 52, 214, 2011 Lambert et al, Blood 115, 2010

18. Role of LDH after allogeneic SCT for NHL Kenkre et al, Leukemia and Lymphoma, 52, 214, 2011 Armand et al, BBMT 14: 418, 2008

19. Misconcep·tion Many with less than partial responses to salvage therapy will achieve durable remissions from high dose chemotherapy and autologous or allogeneic transplant. Delays in treatment from investigational treatments may adversely affect long-term outcome….

20. The future… combination

21. Refractory Lymphoma: Benda Bridge to TX

22. Dubovsky et al, JCI, 2014