Management of Severe Immune-Related Adverse Events With Ipilimumab/Nivolumab and Survival in Advanced Melanoma

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In a Dutch study reported in JAMA Oncology, van Not et al found that management of grade ≥ 3 immune-related adverse events with steroids alone vs steroids plus second-line immunosuppressants was associated with better survival outcomes among patients receiving first-line combination ipilimumab and nivolumab for advanced melanoma.

Study Details

The population-based, multicenter cohort study included data from the Dutch Melanoma Treatment Registry on patients receiving first-line ipilimumab/nivolumab between 2015 and 2021.  

Key Findings

Among 771 patients treated with first-line ipilimumab/nivolumab, 385 (49.9%) experienced grade ≥ 3 immune-related adverse events. Of these, 350 received immunosuppressive treatment, with 235 receiving steroids alone and 115 receiving steroids plus second-line immunosuppressants (tumor necrosis factor inhibitors in 67 and others in 35). Colitis (n = 146) and hepatitis (n = 139) were the most common adverse events.

Median follow-up was 23.6 months. Compared with patients receiving steroids alone, those receiving steroids plus second-line immunosuppressants had worse progression-free survival (median = 5.4 months, 95% confidence interval [CI] = 4.5­–12.4 months, vs 11.3 months, 95% CI = 9.6–19.6 months; hazard ratio [HR] = 1.43, 95% CI = 1.07–1.90, P = .01); overall survival (median = 22.5 months, 95% CI = 36.5 months to not reached, vs not reached, vs 46.1 months, 95% CI = 39.0 months to not reached, HR = 1.62, 95% CI = 1.07–2.46, P = .02); and melanoma-specific survival (median = 28.8 months, 95% CI = 20.5 months to not reached, vs not reached, 95% CI = 46.1 months to not reached, P = .006).

On multivariate analysis adjusting for potential confounders, patients receiving steroids plus second-line immunosuppressants had borderline significant poorer progression-free survival (adjusted HR = 1.40, 95% CI = 1.00–1.97, P = .05) and significantly poorer overall survival (adjusted HR = 1.54, 95% CI =1.03–2.30, P = .04).

The investigators concluded, “In this cohort study, second-line immunosuppression for immune-related adverse events was associated with impaired progression-free survival, overall survival, and melanoma-specific survival in patients with advanced melanoma treated with first-line ipilimumab and nivolumab. These findings stress the importance of assessing the effects of differential immune-related adverse event management strategies, not only in patients with melanoma but also other tumor types.”

Olivier J. van Not, MD, of the Department of Medical Oncology, University Medical Centre Utrecht, Utrecht University, is the corresponding author for the JAMA Oncology article.

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