Safety of Bendamustine in Chronic Lymphocytic Leukemia and Non-Hodgkin Lymphoma

Julie M. Vose, MD, MBA

The previous articles have outlined the clinical outcomes of clinical trials evaluating bendamustine in chronic lymphocytic leukemia (CLL) and non-Hodg­kin lymphoma (NHL). The third in the series of articles discusses the short-term toxicities of bendamustine from these clinical trials.

Patients with CLL are always a challenge to treat due to their underlying immune suppression. Compared with chlorambucil, patients receiving bendamustine had higher rate of grade 3/4 neutropenia – 43% versus 21%. Grade 3/4 thrombocytopenia was almost identical – 10% for chlor­ambucil and 11% for bendamustine, and the infection rate was similar in the 2 arms. Nonhematologic toxicities were also similar between the arms. With similar toxicities but an improved response rate, bendamustine has be­­come a frequently used alternative for patients with CLL.

In patients with indolent NHL, the pooled safety data showed the most common serious adverse events to be febrile neutropenia and pneumonia. Other grade 3/4 adverse events of note were fatigue (11%), hypokalemia (5%), and dehydration (5%). Varicella zoster reactivation was seen in 11% of patients who did not take antiviral prophylaxis but was controlled in those who did take it. Patients with prior purine analogue therapy had an increased risk of grade 3/4 neutropenia (41% vs 29%). Appropriate prophylactic antibiotics do need to be used in patients receiving bendamustine.

Infections are common in patients with CLL and NHL despite aggressive supportive care such as neupogen or neulasta and prophylactic antibiotics. If a patient has been heavily pretreated, has a lower neutrophil count, or has a bad performance status, a first-cycle dose reduction of bendamustine should be considered. A high level of suspicion for cytopenias and infectious complications should be maintained for patients receiving bendamustine. Other more rare complications include infusion reaction, rash, or tumor lysis. Because bendamustine does damage DNA, there is the potential for secondary malignancies as well. However, when weighing the risk/benefit ratio, bendamustine is a beneficial drug for many patients with CLL and NHL.

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Last modified: May 21, 2015