Retrospective analysis of nivolumab maintenance after severe immune-related adverse events on nivolumab plus ipilimumab for advanced melanoma

The combination of nivolumab plus ipilimumab is a highly effective treatment for metastatic cutaneous melanoma. However, immune-related adverse events (irAEs) are common, often necessitating treatment interruption and the use of immunosuppressive agents. A retrospective analysis of patients of Dana-Farber Cancer Institute (Boston, MA) evaluated nivolumab maintenance after recovery from the irAE and completion of immunosuppressive treatment. Among 122 advanced melanoma patients recovered from the irAE caused by nivolumab plus ipilimumab, 46 resumed single-agent nivolumab. When stratified by age and adjusted for sex, M-stage, LDH, therapy duration, and irAE type, the effect of resumption of nivolumab on survival was highly significant (p=0.02). Patient who resumed nivolumab had a 68% reduction in the hazard of death compared with patients who had not yet or never resumed nivolumab (HR 0.32; 95% CI 0.12-0.84). Of the patients who resumed nivolumab, 26% had subsequent irAEs, with 11% having grade 3 irAEs. No grade 4 or 5 irAEs were observed. The authors conclude that resuming single-agent nivolumab after treatment interruption for nivolumab/ipilimumab-associated irAE and completion of immunosuppressive therapy increased overall survival compared with discontinuing nivolumab permanently in patients with metastatic melanoma.