Bendamustine Is Highly Active in Heavily Pre-Treated Relapsed and Refractory Hodgkin Lymphoma and Serves as a Bridge to Allogeneic Stem Cell Transplant.

No standard treatment exists for relapsed or refractory (rel/ref) Hodgkin lymphoma (HL) following autologous stem cell transplant (ASCT) failure and prognosis is poor. Nonmyeloablative allogeneic stem cell transplant (NMT) offers a chance of cure in a subset of these patients; therefore the goal of treatment should be to ultimately refer patients to NMT. Bendamustine is a bifunctional alkylating agent, recently FDA approved for the treatment of chronic lymphocytic leukemia and indolent B-cell non-Hodgkin lymphoma. Limited data supports the use of bendamustine in HL (Borchmann, et al. Ann Oncol 1998).

This is a phase II clinical trial evaluating the activity of single-agent bendamustine in rel/ref HL for ASCT failures, NMT failures, or patients (pts) who are ineligible for transplant. Our primary outcomes are response rate and, for eligible pts, referral to NMT. Pts receive bendamustine 120mg/m2, for two consecutive days, every 28 days. Pegfilgrastim is administered with each cycle and treatment is delayed until absolute neutrophil count is > 1000/ul and the platelet count is > 75,000/ul. Dose is reduced to 100mg/m2 in cases of treatment delays > 5 days due to neutropenia or thrombocytopenia or for grade 3 non-hematologic toxicities. Pts are evaluated for response by CT and PET after 2, 4, and 6 cycles. Pts deemed eligible for NMT at initiation of bendamustine are referred when they have had maximal response to bendamustine. Others receive a maximum of 6 cycles.

To date, 18 out of a planned 37 pts have been enrolled. Twelve of the 18 pts previously failed ASCT, 2 failed NMT. Of 16 evaluable pts, 2 progressed prior to the first re-evaluation and died rapidly from HL. Of the remaining 14 pts, 12 pts responded. There were 6 CRs (38%), 6 PRs (38%), 1 SD; ORR was 75%. All responding pts showed evidence of improvement at first restaging. One pt withdrew consent after 1 cycle. This pt achieved a CR and has been monitored off therapy for 10 months. At time of enrollment, 12 of the 16 evaluable pts were deemed eligible for NMT. Reasons for NMT ineligibility were additional comorbidities (3) and previous NMT (1). Of the 12 NMT eligible pts, 3 have completed NMT and 3 were referred but ultimately refused. The three completed NMTs were performed following 4 cycles of bendamustine. Bendamustine was very well tolerated. Three SAEs have occurred: grade 3 nausea following cycle 1, fungal pneumonia following cycle 2, and pyelonephritis following cycle 6. There have been 6 treatment delays due to thrombocytopenia (3), neutropenia (1), pneumonia (2). There have been 4 treatment reductions due to neutropenia (2), nausea (1), and thrombocytopenia (1).

Interim results from this ongoing trial indicate that bendamustine is highly active in heavily pre-treated rel/ref HL and enables referral to NMT in a significant portion of eligible pts. Future studies will combine bendamustine with novel agents in rel/ref HL.

No relevant conflicts of interest to declare.