The discovery and the development of bendamustine for the treatment of non-Hodgkin lymphoma

ABSTRACT

Introduction: Non-Hodgkin lymphoma (NHL) is a heterogeneous group of lymphoid malignancies. The treatment strategy for patients with NHL had remained unchanged until the advent of the era of molecular targeting agents. Although rituximab-containing chemotherapy has improved the response rates and survival of patients with B-cell NHL (B-NHL), several subtypes of B-NHL, especially indolent B-NHL and mantle cell lymphoma (MCL), remain incurable. Therefore, novel treatment modalities for B-NHL, especially for indolent B-NHL and MCL, are needed. Bendamustine is an old, but unique, multifunctional cytotoxic agent that exhibits structural similarity to alkylating agents and purine analogs.

Areas covered: The basic aspects and preclinical development of bendamustine are summarized, followed by a discussion of the clinical development of bendamustine-based treatments for indolent B-NHL and MCL.

Expert opinion: Bendamustine monotherapy or the use of bendamustine in combination with rituximab is highly effective against various types of hematological malignancies, especially relapsed or refractory indolent B-NHL, and exhibits an acceptable toxicity profile. Furthermore, bendamustine plus rituximab might be a promising treatment option for patients with untreated indolent B-NHL. Therefore, bendamustine has the potential to play an important role in the treatment of malignant lymphoma.

KEYWORDS:

• Bendamustine
• malignant lymphoma
• indolent B-cell non-Hodgkin lymphoma
• follicular lymphoma
• mantle cell lymphoma

Article highlights

• Bendamustine is an old, but unique multifunctional cytotoxic agent that exhibits structural similarity to alkylating agents and antimetabolites.

• It has demonstrated clinical activity against various types of hematological malignancies, especially indolent B-NHL and MCL.

• Bendamustine is generally well tolerated. Furthermore, the toxicity profiles of bendamustine-containing regimens and conventional chemoimmunotherapies are different.

• Bendamustine is expected to serve as a backbone for the future development of novel regimens, including new molecular targeting agents.

• The results of bendamustine in combination with molecular targeting agents, such as ibrutinib and lenalidomide, have been reported and showed a promising efficacy.

• Future clinical studies are needed to investigate suitable molecular targeting agents in combination with bendamustine.

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Declaration of interest

K Tobinai received research funding and honoraria from Eisai Co., Ltd that sells bendamustine. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This work was supported in part by the National Cancer Center Research Fund 26-A-4.