Bendamustine: Rebirth of an Old Drug

Abstract

Bendamustine is a unique cytotoxic agent with structural similarities to alkylating agents and antimetabolites, but which is non-cross-resistant with alkylating agents and other drugs in vitro and in the clinic. Early clinical studies conducted in the German Democratic Republic more than 30 years ago suggested promising activity in indolent non-Hodgkin's lymphoma (NHL). Two North American trials reported responses in more than 70% of patients with chemotherapy- and rituximab-refractory disease, suggesting that bendamustine may be the most effective drug available for this patient population. Response rates of 90% to 92%, with complete remission in 55% to 60%, have been reported in patients with follicular and mantle-cell lymphoma with the combination of bendamustine and rituximab. Superiority over chlorambucil in previously untreated patients with chronic lymphocytic leukemia (CLL) led to its recent approval for this disease in the United States. Bendamustine is approved in Germany for the treatment of patients with indolent NHL, CLL, and multiple myeloma. Activity has also been noted in patients with breast cancer and small-cell lung cancer [corrected]. Questions related to the optimization of bendamustine therapy, including dose and schedule, role relative to other available agents, and management of toxicities, are being investigated. However, the availability of bendamustine provides another effective treatment option for patients with lymphoid malignancies.

Novel therapeutic agents for B-cell lymphoma: developing rational combinations

“…DNA damage is more extensive and it occurs with slower and different DNA repair pathways than other alkylators. 72,73 Use in lymphoma. A phase 2 trial of bendamustine in patients with rituximab-refractory or -intolerant, -indolent, or -transformed lymphoma showed an overall response of 77%.…”

The combination of rituximab, bendamustine, and cytarabine for heavily pretreated relapsed/refractory cytogenetically high‐risk patients with chronic lymphocytic leukemia

“…Bendamustine is an alkylating agent that has purine analogue properties and exhibits considerable activity in indolent lymphomas and CLL [13,14]. It has been reported that bendamustine exerts a cytotoxic effect in CLL cell lines, involving both p53-dependent and p53-independent mechanisms [15].…”

Combinations of idelalisib with rituximab and/or bendamustine in patients with recurrent indolent non-Hodgkin lymphoma

“…Patients were treated in 1 of 3 cohorts based on investigator's choice and received continuous oral therapy with idelalisib. 4 The treatment groups received either rituximab (IV infusion of 375 mg/m 2 weekly for 8 doses), bendamustine (30-minute IV infusion of 90 mg/m 2 on days 1 and 2), or the combination of bendamustine and rituximab (bendamustine at 90 mg/m 2 on days 1 and 2, then rituximab at 375 mg/m 2 on day 1), and all groups received twice-daily idelalisib. Idelalisib was provided as 100-or 150-mg tablets, with 75-and 50-mg tablets available for dose reductions.…”

“…1,2 Treating recurrent iNHL continues to be challenging. Current therapies commonly include anti-cluster of differentiation 20 antibodies, such as rituximab 3 (US approval in 1997) and the alkylator bendamustine 4 (US approval in 2008), which have demonstrated activity and tolerability in combination with rituximab. 5 Although initially effective for iNHL, standard chemotherapy and immunotherapy generally demonstrate decreasing efficacy with repeated administration.…”