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

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

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– Transplantation Conventional treatment P = Transplantation (n = 49) Conventional treatment (n = 54) P = Months after randomization Event-free survival Overall survival Survival (%)

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)

What are the Data?

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

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

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

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

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

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

Probability Of Relapse After Syngeneic Transplantation PROBABILITY, % YEARS ASC01_9.ppt Allo T-deplete Auto unpurged Allo T-replete Auto purged Syngeneic P < patients syngeneic transplant. 30 intermediate grade lymphoma Bierman et al, J Clin Oncol 21, 3744, 2003

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

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

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)

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…

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

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

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….

The future… combination

Refractory Lymphoma: Benda Bridge to TX

Dubovsky et al, JCI, 2014