Bendamustine: A review of pharmacology, clinical use and immunological effects (Review)

Abstract

Bendamustine is an alkylating agent classified into the group of nitrogen mustard analogues, synthesized almost sixty years ago. It was registered in former East Germany in 1971 and approved by the US Food and Drug Administration in 2008 for treatment of chronic lymphocytic leukemia and indolent B‑cell non‑Hodgkin lymphoma. Considering its beneficial properties in the therapy of relapsed or refractory hematological malignancies, synergistic effects with other antineoplastic agents and increasing recent reports on its immunomodulatory effects, bendamustine has once again gained its justified attention. The uniqueness of bendamustine‑mediated effects should be observed keeping in mind its distinctive structure with structural similarities to both alkylating agents and purine analogs. In the present review, the current knowledge on the use of bendamustine in oncology, its pharmacokinetics, mechanism of action and toxicity was summarized. In addition, its immune‑modulating effects that have not been fully elucidated so far are emphasized, hoping to encourage further investigations of this unique drug.

Keywords: B‑cell; B‑cell chronic lymphocytic leukemia; T‑cell; bendamustine hydrochloride; cell cycle; cell death; immunomodulation; lymphocytes; non‑Hodgkin lymphoma.

Figure 1.

Chemical structure of bendamustine and similarities with other alkylating drugs.

Figure 2.

Potential mechanism of action of bendamustine. The figure was created with BioRender.com.

Figure 3.

Bendamustine-mediated effects on immune cells. The figure was created with BioRender.com. Tregs, regulatory T cells; cDCs, conventional dendritic cells; ADCC, antibody-dependent cell cytotoxicity; pDC, plasmacytoid dendritic cells.