Brentuximab Vedotin-Induced Peripheral Neuropathy

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Treatment with brentuximab vedotin is associated with several side effects, including peripheral neuropathy, notes moderator Myron S. Czuczman, MD. In the phase II study that was the basis for the accelerated approval of brentuximab vedotin, patients received several therapies prior to the study, notes Anas Younes, MD. In some cases, patients had received ABVD, platinum-based regimens, and other neurotoxic agents, resulting in a higher than expected incidence of neuropathy, suggest Younes.

In the study, the rate of all grade peripheral sensory neuropathy was 52% and the rate of peripheral motor neuropathy was 16%. In general, brentuximab vedotin-induced neuropathy appears to be cumulative and can be reversed through dose discontinuation, modification, or interruptions, Younes suggests.

Studies have indicated that severe neuropathy occurs after 7 to 9 cycles of treatment, suggesting a cumulative effect, notes Andrei R. Shustov, MD. At this point, treatments for neuropathic pain, such as gabapentin (Neurontin), have not demonstrated efficacy as prophylactic measures in clinical trials, notes Younes.

In patients refractory to autologous and allogeneic transplantation it is difficult to stop a treatment that is working as a result of side effects, notes Czuczman. However, Pinter-Brown adds, if a patient is responding to brentuximab prior to a treatment holiday they will continue to respond when rechallenged.

In addition to neuropathy, Steve M. Horwitz, MD, suggests that treatment with brentuximab vedotin may be associated with pancreatitis in some patients. Moreover, Lauren C. Pinter-Brown, MD, notes a higher than expected incidence of alopecia.

Following the approval, the FDA added a Boxed Warning to brentuximab vedotin’s label highlighting the risk of developing progressive multifocal leukoencephalopathy. Despite the CD30 specificity for brentuximab vedotin, the design of the linker allows it to be cleaved by the lysosome, allowing for a possible impact on the tumor microenvironment, Younes notes.