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Bendamustine

A Review of its Use in the Management of Chronic Lymphocytic Leukaemia, Rituximab-Refractory Indolent Non-Hodgkin’s Lymphoma and Multiple Myeloma

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Abstract

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.

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    Sheridan M. Hoy

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Correspondence to Sheridan M. Hoy.

Additional information

Various sections of the manuscript reviewed by: J.R. Berenson, Hematology/Oncology, Institute for Myeloma & Bone Cancer Research, West Hollywood, CA, USA; W. Knauf, Onkologische Gemeinschaftspraxis, Frankfurter Diakonie Kliniken, Frankfurt, Germany; M. Montillo, Department of Oncology/Haematology, Division of Haematology, Niguarda Ca’ Granda Hospital, Milan, Italy; L. Rigacci, Division of Hematology and Bone Marrow Transplantation, Azienda Ospedaliera Universitaria Careggi, Florence, Italy; T. Robak, Department of Haematology, Medical University of Lodz, Lodz, Poland; R.H.C. van der Jagt, Ottawa Health Research Institute, Ottawa Hospital, Ottawa, ON, Canada.

Data Selection

Sources: Medical literature (including published and unpublished data) on ‘bendamustine’ was identified by searching databases (including MEDLINE and EMBASE) for articles published since 1996, bibliographies from published literature, clinical trial registries/databases and websites (including those of regional regulatory agencies and the manufacturer). Additional information (including contributory unpublished data) was also requested from the company developing the drug.

Search strategy: MEDLINE and EMBASE search terms were ‘bendamustine’ and ([‘chronic lymphocytic leukaemia’ or ‘chronic lymphocytic leukemia’ or ‘CLL’] or [‘multiple myeloma’] or [‘NHL’ or ‘non-Hodgkin’]). Searches were last updated 3 September 2012.

Selection: Studies in patients with chronic lymphocytic leukaemia, indolent non-Hodgkin’s lymphoma or multiple myeloma who received bendamustine. Inclusion of studies was based mainly on the methods section of the trials. When available, large, well controlled trials with appropriate statistical methodology were preferred. Relevant pharmacodynamic and pharmacokinetic data are also included.

Index terms: Bendamustine, chronic lymphocytic leukaemia, multiple myeloma, indolent non-Hodgkin’s lymphoma, pharmacodynamics, pharmacokinetics, therapeutic use.

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Hoy, S.M. Bendamustine. Drugs 72, 1929–1950 (2012). https://doi.org/10.2165/11209510-000000000-00000

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