Bendamustine is a chemotherapy medicine that is approved in the U.S. for the treatment of chronic lymphocytic leukemia (CLL) and indolent B-cell non-Hodgkin’s lymphoma (NHL). In Europe, the medicine also may be used in combination with prednisone to treat patients with newly diagnosed multiple myeloma.
How does bendamustine work?
Bendamustine is a purine analog similar to cladribine and fludarabine. Purine analog are medicines that mimic the structure of a building block of DNA called purines. DNA to which a purine analog is incorporated, instead of the original purines, fails to replicate. This eventually causes cell death.
Bendamustine also is an alkylating agent. Alkylating agents add a molecule called an alkyl group to the DNA molecule, which also prevents it from replicating or breaks it, resulting in cell death either via apoptosis or a non-apoptotic mechanism in both non-dividing and dividing cells.
Bendamustine in clinical trials
While bendamustine is effective on its own as a monotherapy, several clinical trials have shown that it is more effective when given in combination with other anti-cancer treatments.
A clinical trial in Germany to assess the safety and effectiveness of bendamustine in combination with Velcade (bortezomib) and prednisone for the treatment of newly diagnosed multiple myeloma patients was completed in 2013. The results showed that the combination treatment was well-tolerated and showed rapid responses in those patients.
A multi-center, randomized, dose selection Phase 2 clinical trial called  MUKone (ISRCTN90889843) tested a combination of bendamustine, Thalomid (thalidomide), and dexamethasone to treat patients with relapsed or refractory multiple myeloma (RRMM). The trial was completed in 2013 and data showed that a 60 mg per square meter dose of bendamustine in combination with Thalomid and dexamethasone was tolerable in those patients with a partial response rate of 41% and a 12-month progression-free survival rate greater than 15%.
A Phase 1/2 dose expansion clinical trial (NCT01754402) to study the maximum tolerated dose and initial response rate of a combination of bendamustine, Pomalyst (pomalidomide), and dexamethasone in patients with RRMM who have undergone prior Revlimid therapy, is expected to be completed in January 2023. Initial results showed that the combination is tolerable and could achieve an overall response rate (ORR) of 72%. The study also showed that a significant number of patients experienced adverse events (side effects) such as neutropenia, anemia, and diarrhea.
A Phase 1/2 clinical trial (NCT02002598) to determine the dose-limiting toxicity and effectiveness of a combination of bendamustine, Kyprolis (carfilzomib), and dexamethasone in newly diagnosed multiple myeloma  patients was completed in March 2019. The results showed an 89% rate of complete response or very good partial response, indicating this combination to be an effective induction therapy for MM.
A Phase 1/2 dose-escalation clinical trial (NCT02477215) to study the combination of bendamustine, Ninlaro (ixazomib), and dexamethasone in RRMM patients who have not responded to autologous hematopoietic stem cell transplantation (AHSCT), or are ineligible for that therapy, is expected to be completed in May 2020. Preliminary results indicate this combination has an acceptable safety profile with an ORR of 45% and a clinical benefit rate of 73% in RRMM patients.
Possible side effects
Common side effects of bendamustine therapy include fever, neutropenia, skin rash, and chills. Infection, pneumonia, and severe itching also have been reported.
Last updated: Dec. 4, 2019
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