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. Contents 1. Introduction 2. Bendamustine-mechanism of action, cell death, and cell cycle 3. Bendamustine-pharmacokinetics 4. Bendamustine in hematological and solid malignancies 5. Bendamustine-related side-effects in clinical trials 6. Immunological effects of bendamustine 7. Conclusion

Efficacy and Safety of Obinutuzumab-chemotherapy Combinations in Front-line Treatment of Follicular Non-Hodgkin Lymphoma During the COVID-19 Pandemic: A Study of KROHEM, the Croatian Cooperative Group for Hematologic Diseases

“…Despite the fact that bendamustine is an old drug, the immunological consequences of its use are still incompletely understood, but include prolonged B‐ and T‐lymphocyte depletion 21 . The latter is probably the most important cause of increased mortality due to infections seen in our series and in the GALLIUM study, since neutropenia and hypogammaglobulinemia were similar in patients treated with G‐CHOP and G‐B.…”

BR or R-CHOP induction followed by rituximab maintenance in transplant-ineligible patients with mantle cell lymphoma

“…For individuals aged 65 and above who are ineligible for intensive treatment, including autologous stem-cell transplantation (ASCT), due to comorbidities, the combination of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) has been a common induction regimen for at least two decades now (4). Bendamustine in combination with rituximab (BR) is an established standard rst-line therapy alternative to R-CHOP (1,4) BR is generally associated with a very low rate of alopecia among others but carries a higher risk of lymphopenia compared to R-CHOP (5).…”

Novel 7-Chloro-4-aminoquinoline-benzimidazole Hybrids as Inhibitors of Cancer Cells Growth: Synthesis, Antiproliferative Activity, in Silico ADME Predictions, and Docking

“…It has demonstrated clinical activity against hematologic malignancies when used as a monotherapy or in combination with other chemotherapeutics. It is currently indicated for the treatment of chronic lymphocytic leukemia (CLL) and indolent B cell non-Hodgkin’s lymphoma (NHL) [ 13 , 14 ]. The next important antitumor drug with a benzimidazole moiety is Binimetinib ( Figure 1 ), whose mechanism of action is related to the inhibition of mitogen-activated protein kinases (MEK-1 and 2).…”