Long‐term outcomes, secondary malignancies and stem cell collection following bendamustine in patients with previously treated non‐Hodgkin lymphoma

Abstract

Despite the long history of bendamustineas treatment for indolent non-Hodgkin lymphoma (iNHL), long-term efficacy and toxicity data are minimal. We reviewed long-term data from three clinical trials to characterize toxicity and efficacy of patients receiving bendamustine. Data were available for 149 subjects at 21 sites. The median age was 60 years at the start of bendamustine (range 39-84), and patients had received a median of 3 prior therapies. The histologies included grade 1-2 follicular lymphoma (FL; n=73), grade 3 FL (n=23), small lymphocytic lymphoma (SLL; n=20), marginal zone lymphoma (MZL; n=15), mantle cell lymphoma (n=9), transformed lymphomas (n=5), lymphoplasmacytic lymphoma (n=2), and not reported (n=2). The median event-free survival was 14.1 months. Nine of 12 attempted stem cell collections were successful. With a median follow-up of 8.9 years, 23 patients developed 25 cancers, including 8 patients with myelodysplastic syndrome/acute myeloid leukemia. These data provide important information regarding the long-term toxicity of bendamustine in previously treated patients. A small but meaningful number of patients achieved durable remissions following bendamustine. These rigorously collected, patient-level, long-term follow-up data provide reassurance that bendamustine or bendamustine plus rituximab is associated with efficacy and safety for patients with relapsed or refractory iNHL.

Risk of secondary haematological malignancies in patients with follicular lymphoma: an analysis of 1028 patients treated in the rituximab era

“…SHMs are associated with the use of alkylating agents, topoisomerase inhibitors and radiation therapy. In a previous study of 149 NHL patients that had received bendamustine at some point in their treatment, the cumulative incidence rate of MDS/AML was reported to be 6·2% with a median follow‐up of 8·9 years (Martin et al , ). The median time to MDS/AML after NHL diagnosis was 89 months.…”

“…These patients had been treated with multiple lines of treatment and the median number of prior therapies before bendamustine was three. No clear association between bendamustine dosage and secondary MDS/AML was found (Martin et al , ). In our study, the use of bendamustine was not found to be associated with a higher risk of SHM although the number of such patients was limited.…”

Prospective Clinical Trial of Ixazomib, Dexamethasone, and Rituximab as Primary Therapy in Waldenström Macroglobulinemia

“…Both treatment regimens are highly efficacious with fast responses, ORR of over 90%, and prolonged PFS (17)(18)(19). In terms of safety, however, bendamustine has been associated with a small risk of secondary myeloid malignancies and myelodysplasia (20), which should be taken into account, especially in younger patients with WM. Ibrutinib also carries a distinct toxicity profile with increased risk of bleeding and atrial fibrillation (17,19).…”

Waldenstrom’s Macroglobulinemia: An Update

“…With a median follow-up of 8·9 years, 23/149 patients developed 25 cancers, including 8 patients with myelodysplastic syndrome/acute myeloid leukaemia. 107 …”