What is it about?

This case demonstrates that toxicity may occur in association with pembrolizumab treatment after a prolonged period of treatment without toxicity. Future trials should explore the optimal duration of treatment with pembrolizumab. Cancer Immunol Res; 4(3); 175–8. ©2016 AACR.

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Why is it important?

Checkpoint inhibitors have significantly improved survival outcomes in metastatic melanoma. More recently, the PD-1 antibodies pembrolizumab and nivolumab were both approved for treatment-refractory metastatic melanoma after ipilimumab failure. Emerging data from the Keynote-006 comparative study of ipilimumab (a CTLA-4 inhibitor) and pembrolizumab have shown superiority of first-line pembrolizumab in response rates and survival. However, the optimal duration of treatment with anti–PD-1 agents is unknown. The majority of toxicities, particularly immune-related adverse events, appear to occur in the first 6 months of treatment, but toxicity may occur later with ongoing therapy.

Perspectives

Here, we report the case of a 51-year-old woman with M1c metastatic melanoma whom we treated with pembrolizumab as first-line treatment for metastatic disease. This patient had a complete radiologic response to pembrolizumab with no adverse events during 18 months of treatment. One month after discontinuation of treatment, she presented with eosinophilic fasciitis and went on to develop acute confusion presumed to be due to cerebral vasculitis. The durability of pembrolizumab responses is unknown. Future trials must explore different schedules of treatment to determine the optimal treatment duration. Continued monitoring of patients on anti–PD-1 inhibitors will determine the risk of delayed toxicity, its severity, and reversibility.

Dr Catherine Maurice
University of Toronto

Read the Original

This page is a summary of: Eosinophilic Fasciitis and Acute Encephalopathy Toxicity from Pembrolizumab Treatment of a Patient with Metastatic Melanoma, Cancer Immunology Research, January 2016, American Association for Cancer Research (AACR), DOI: 10.1158/2326-6066.cir-15-0186.
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