Bendamustine: a review of its use in the management of chronic lymphocytic leukaemia, rituximab-refractory indolent non-Hodgkin's lymphoma and multiple myeloma.

Bendamustine (Levact®) is an alkylating agent consisting of three structural elements: a 2-chloroethylamine alkylating group; a butyric acid side chain; and a benzimidazole ring. Although its precise mechanism of action is as yet unknown, it appears to exert its antineoplastic effects via a different mechanism to those of other alkylating agents. This article reviews the utilization of intravenous bendamustine in patients with chronic lymphocytic leukaemia (CLL), rituximab-refractory indolent non-Hodgkin's lymphoma (NHL) and multiple myeloma (MM), focusing on indications for which the agent is approved in the EU. As monotherapy, bendamustine was effective in the first-line treatment of adults with CLL, significantly prolonging progression-free survival (PFS) and improving the overall response (OR) rate after a median duration of follow-up of 35 months compared with chlorambucil in a randomized, open-label, multinational, phase III study. PFS and the OR rate were at least 2-fold greater with bendamustine than with chlorambucil when data from the overall patient population were stratified by Binet stage. In the treatment of adults with rituximab-refractory indolent NHL, monotherapy with bendamustine was efficacious, with an OR achieved by at least three-quarters of patients in two noncomparative multicentre studies. Patients with follicular histology or those who had responded or were refractory to their previous chemotherapy regimen (including alkylator therapy) also appeared to respond to bendamustine monotherapy. Front-line combination therapy with bendamustine plus prednisone was significantly more effective than combination therapy with melphalan plus prednisone in prolonging the time to treatment failure, according to a randomized, open-label multicentre, phase III study in adults with MM. Moreover, the benefits of bendamustine plus prednisone appeared to be maintained beyond 30 months, with a retrospective calculation of PFS demonstrating a borderline statistical significance in favour of bendamustine plus prednisone over melphalan plus prednisone. The tolerability profile of bendamustine in adults with CLL, indolent NHL or MM was mostly consistent with the known toxicities of the agent, with adverse events often managed with dose modifications. Although further data are required to fully establish the comparative efficacy of intravenous bendamustine in the management of CLL, rituximab-refractory indolent NHL or MM, it appears to be a useful addition to the armamentarium of currently available therapies for these haematological malignancies.