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What Is Bendamustine and To Whom Is It Given?

TREANDA® or BENDEKA® (bendamustine) is a type of FDA-approved chemotherapy to treat chronic lymphocytic leukemia (CLL) and indolent B-cell non-Hodgkin lymphoma (NHL) in the U.S. It has been approved in Europe as a first-line treatment for multiple myeloma in combination with prednisone for patients older than 65 years who are not eligible for autologous stem cell transplant, and who have peripheral neuropathy at the time of diagnosis. Because these patients live with peripheral neuropathy, they are unable to use Thalomid (thalidomide) or Velcade (bortezomib) treatment regimens. It is a cytotoxic agent with combined activity of alkylating agent and purine analog. Many studies show that it is an effective treatment in relapsed/refractory multiple myeloma (RRMM), and it is recognized as a treatment option by the National Comprehensive Cancer Network (NCCN) when used in combination therapy. Bendamustine may impact the ability to collect T cells prior to CAR T-cell therapy, so caution should be used. 

How Is Bendamustine Given?

Bendamustine is given intravenously (through an injection). Its dosing varies depending on the reason why it is being administered. For full details, consult with your healthcare provider and reference the prescribing information here

How Does Bendamustine Work? 

Bendamustine functions as a purine analog. Purine analogs are pharmaceutical compounds that emulate the structural composition of purines, the fundamental building blocks of DNA. When DNA incorporates a purine analog instead of the native purines, the replication process is hindered. Ultimately, this leads to cell death. 

Additionally, bendamustine serves as an alkylating agent. Alkylating agents introduce an alkyl group into the DNA molecule. As a result, its replication is impeded, or structural breaks are caused. This disruption results in cell death through either apoptosis or a non-apoptotic mechanism, affecting both actively dividing and non-dividing cells. 

What Are the Potential Side Effects of Bendamustine?

Bendamustine can cause severe side effects in some people. See the bendmustine prescribing information for full details. The most common side effects of bendamustine for multiple myeloma patients include: 

  • Chills 
  • Deep vein thrombosis (blood clot) 
  • Fever 
  • Infection including pneumonia 
  • Low white blood cell count (neutropenia) 
  • Skin rash 

How Is Bendamustine Being Used in Clinical Trials?

Bendamustine is often used as a standalone therapy. Yet, it has shown even greater efficacy when combined with other anti-cancer treatments, according to several clinical trials. 

In a clinical trial conducted in Germany in 2013, bendamustine was used in combination with Velcade (bortezomib) and prednisone to treat newly diagnosed multiple myeloma patients. The results demonstrated that this combination treatment was well-tolerated and led to rapid responses in patients. 

Another clinical trial, called MUKone, was a multicenter, randomized, dose selection phase II trial that tested a combination of bendamustine, Thalomid (thalidomide), and dexamethasone for patients with relapsed or refractory multiple myeloma (RRMM). The trial, completed in 2013, revealed that a 60 mg per square meter dose of bendamustine in combination with Thalomid and dexamethasone was tolerable in patients, with a partial response rate of 41% and a 12-month progression-free survival rate of over 15%. 

A phase I/II dose-expansion clinical trial, expected to be completed in January 2023, is studying the maximum tolerated dose and initial response rate of combining bendamustine, Pomalyst (pomalidomide), and dexamethasone in RRMM patients who have previously undergone Revlimid (lenalidomide) therapy. Initial results indicate that this combination is tolerable and could achieve an overall response rate (ORR) of 72%. However, it was also found that a significant number of patients experienced adverse events such as neutropenia, anemia, and diarrhea. 

A completed phase I/II clinical trial in March 2019 evaluated the dose-limiting toxicity and effectiveness of combining bendamustine, Kyprolis (carfilzomib), and dexamethasone in newly diagnosed multiple myeloma patients. The results were promising, with an 89% rate of complete response or very good partial response, suggesting that this combination is a highly effective induction therapy for multiple myeloma. 

The ongoing phase I/II dose-escalation clinical trial, set to be completed in May 2020, is studying the combination of bendamustine, Ninlaro (ixazomib), and dexamethasone in RRMM patients who have not responded to autologous stem cell transplant (ASCT), or are ineligible for ASCT. Preliminary results indicate that this combination has an acceptable safety profile, with an overall response rate of 45% and a clinical benefit rate of 73% in RRMM patients. 

 


 


The International Myeloma Foundation medical and editorial content team

Comprised of leading medical researchers, hematologists, oncologists, oncology-certified nurses, medical editors, and medical journalists, our team has extensive knowledge of the multiple myeloma treatment and care landscape. Additionally, Dr. Brian G.M. Durie reviews and approves all medical content on this website. 

Last Medical Content Review: May 7, 2024

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