Long-term Safety of Bendamustine

With a median follow up of about 9 years, 23 patients developed 25 secondary cancers, including but not limited to non-melanoma skin cancer, adenocarcinoma of the colon, prostate cancer, and lung cancer.

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Six patients developed myelodysplastic syndrome (MDS) and 2 developed acute myeloid leukemia (AML), for a cumulative incidence rate of 6.2%. Median time to development of MDS/AML was 23 months following bendamustine and 89 months following diagnosis. Patients who developed MDS/AML had received 5 median prior therapies inclusive of bendamustine.

“The attention to second cancers was important because bendamustine is an effective alkylating agent and it was important to determine whether secondary malignancies were higher than expected,” Dr Martin said.

“We did not see a high rate of MDS/AML,” he said. The limitation of many prior studies looking at secondary studies is the short median follow-up time. “Secondary malignancies typically peak between 5 and 10 years after exposure to alkylating agents,” Dr Martin said.

Given the relatively short time between bendamustine and the diagnosis of MDS/AML, secondary malignancies may be explained by the prior therapies patients received, the study authors suggested.

Twenty-six infections were also reported after bendamustine therapy, but before subsequent therapy. These included sinopulmonary infection, herpes simplex virus/varicella zoster virus, sepsis, and urinary tract infection.

Nadia Khan, MD, assistant professor from the Fox Chase Cancer Center in Philadelphia, Pennsylvania, commented that “we still do not have clarity with respect to infection risk and secondary cancers, and these should be more closely scrutinized in ongoing trials.”

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Dr Khan indicated that the long-term follow up calls attention for closer evaluation of the immune deregulation that occurs post-bendamustine containing therapies. “There have been increased safety signals with respect to sinopulmonary infections and reactivation of herpes simplex virus. Perhaps prospective evaluation in larger trials can help pinpoint the immune deficits that are relevant,” she said.