Bendamustine-Brentuximab: Bridging to Transplant

Background: The use of monoclonal antibodies in combination with chemotherapy for the treatment of lymphoma may improve efficacy by utilizing distinct mechanisms of tumor kill while minimizing overlapping toxicity. Bendamustine, a bifunctional alkylating agent, has been used with Rituximab in indolent non-Hodgkin lymphomas, chronic lymphocytic leukemia, and more recently for the treatment relapsed and refractory diffuse large B-cell lymphomas (DLBCL).

 Brentuximab, a monoclonal antibody targeting CD30, is approved for refractory and relapsed  anaplastic large cell lymphoma, Hodgkin lymphoma relapsed after autologous stem cell transplant and may have efficacy in the treatment of DLBCL which have been shown to express  CD30 in 14-25% of cases.

We report the Mount Sinai Hospital experience using bendamustine and brentuximab (BB) in the treatment of relapsed-refractory lymphomas and its utility as a bridge to transplant.

Methods: Retrospective analysis of the tolerability and outcomes for patients receiving  BB between 2013 and 2014 as part of quality assurance review.

Results:  Seven  patients (1 female)were identified with a median age of 39 (range 34-70).  Diagnoses included  Hodgkin lymphoma (4),  primary mediastinal B-cell lymphoma  (1),  DLCBL (1),  and peripheral T-cell  enteropathy associated type II lymphoma (1 ).   Median time between initial diagnosis and BB was 19 months (range 12-175 months).   Patients received a mean of 4.1 prior lines of therapy (range 2-9) including allogeneic transplantation (1) and autologous transplantation (4).

All patients received 90 mg/m2 of bendamustine and 1.8 mg/kg of brentuximab approximately every 3 weeks for a mean of 2.71 cycles.    Two patients developed sepsis and fungal pneumonia, respectively.   Of 6 patients evaluable for response,  4 had partial response,  1 had mixed response and 1 had PR after 2 cycles, then received a stem cell boost/DLI  but ultimately died from progression of disease (POD).   2 other patients received allogeneic stem transplants and 3 patients are awaiting transplantation.

Conclusion: BB in our heterogeneous and heavily pre-treated population has been well tolerated, has provided disease control, and has enabled patients to be bridged to transplant, both allogeneic  and autologous.

 

Patient	Diagnosis	Age/Sex	# of BB Cycles	Response	Outcome
1	Hodgkin Lymphoma	42/F	3	PR after 2 cycles	Died POD
2	Primary Mediastinal B cell lymphoma	34/M	3	PR after 2 cycles	Alive  S/P cord blood  transplant
3	Hodgkin Lymphoma	41/M	4	PR after 2 cycles	Alive Awaiting allogeneic transplant
4	DLBCL	36/M	4	PR after cycle 2, stable disease after cycle 4	Alive Awaiting allogeneic transplant
5	Hodgkin Lymphoma	36/M	2	Mixed response after 2 cycles	Alive s/p cord blood transplant
6	Hodgkin Lymphoma	39/M	2	Awaiting imaging s/p 2 cycles	Alive Awaiting autologous transplant
7	Peripheral T cell lymphoma, enteropathy associated type 2	70/M	1	N/A	Alive Awaiting  allogeneic transplant