Bendamustine: Progress in Clinical Investigations

Julie M. Vose, MD, MBA

Uncategorized

At the 54th Annual Meeting of the American Society of Hematology, a number of abstracts were presented demonstrating the efficacy and toxicities of bendamustine either alone or in combination with other agents for the treatment of several lymphoid malignancies such as chronic lymphocytic leukemia (CLL) and indolent as well as aggressive non-Hodgkin lymphoma (NHL). In most of these trials, bendamustine was combined with a monoclonal antibody such as rituximab, ofatumumab, or alemtuzumab. In ad­dition, a third agent has now been combined in many of the more recent trials, such as fludarabine in CLL or bortezomib, idelalisib (GS-1101), or cytarabine for NHL. All of these trials demonstrated toxicity that was acceptable and expected, such as mild to moderate neutropenia, anemia, and throm­bocytopenia. The response rates are high in the patients on these trials; however, further follow-up will be needed for the long-term outcomes. Bendamustine is also being evaluated for other uses such as treatment of Hodgkin lymphoma. A few trials in Hodgkin lymphoma are currently available that combine bendamustine with several agents, including lenalidomide, gemcitabine, and brentuximab vedotin. Results from these interesting trials are pending.

More recently, bendamustine has also been evaluated for the treatment of several solid tumors, including small cell lung cancer, ovarian cancer, and metastatic breast cancer. Additional small studies have been performed in patients with soft tissue sarcoma and refractory germ cell neoplasms. The results from these trials are outlined in the article. Bendamustine has also been used as a first-line therapy in patients with multiple myeloma. The patients in this trial had an overall response rate similar to that achieved with standard therapy. Combination therapy with bortezomib or lenalidomide in patients with multiple myeloma has also shown promise. A phase 2 dose-escalation study of bendamustine plus standard high-dose melphalan as a conditioning regimen for autologous stem cell transplantation has also been performed. In this study, bendamustine could be dose escalated to 225 mg/m2 without any added toxicities.

With the demonstrated activity and versatility of bendamustine as well as the ability to combine it with many other active agents, the clinical usefulness of bendamustine may be much broader than the current indication. Future clinical trials will be needed to confirm the reported effectiveness.

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