Neurotoxicity is not uncommon in patients with melanoma treated with immune checkpoint inhibitors such as nivolumab and pembrolizumab, but it may be more common in patients treated with nivolumab plus a CTLA-4-blocking antibody such as ipilimumab, a study published in the journal Annals of Oncology has shown.1
Immunotherapy has transformed the treatment landscape of advanced melanoma in recent years, with both anti-PD-1 antibodies and CTLA-4-blocking agents having been approved for the treatment of unresectable or metastatic melanoma. Clinical trials have shown that the cumulative incidence of neurotoxicity amongst ipilimumab, nivolumab, and pembrolizumab is less than 1%.
Therefore, researchers sought to examine the incidence of neurotoxicity across anti-CTLA-4 and anti-PD-1 antibodies at a single institution with inclusion of data from published clinical trials.
For the study, investigators analyzed data from a total of 352 patients with advanced melanoma treated with nivolumab, pembrolizumab, or the combination of ipilimumab and nivolumab who received care at the Royal Marsden Hospital in London, United Kingdom, between September 2010 and December 2015, and participants of clinical trials.
After a median follow-up of 26.7 months, results showed that 2.8% of patients overall experienced neurologic toxicity ranging in severity from grade 1 to grade 4. In addition, researchers found that toxicity affected both central and peripheral nervous systems, but patterns of presentation varied.
The study further demonstrated that among patients treated with combination immunotherapy, the rate of neurotoxicity was 14%.
Investigators also found that 3 of 5 patients who initiated corticosteroids responded to treatment and 6 patients had made a full recovery at the time of analysis.
The findings suggest that a prompt and considered approach is needed to enhance outcomes in this population who experience treatment-induced neurotoxicity.
1. Spain L, Walls G, Julve M, et al. Neurotoxicity from immune-checkpoint inhibition in the treatment of melanoma: a single centre experience and review of the literature. Ann Oncol. 2016 Oct 25. doi: 10.1093/annonc/mdw558. [Epub ahead of print]