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Importance: Since 2011, many patients with metastatic melanoma have been treated with ipilimumab therapy and have developed severe immune-related adverse events (AEs). Because several immune therapies are now available to treat metastatic melanoma, a better knowledge of mechanisms and recurrence risks of immune-related AEs is needed before reintroduction of immunotherapies., Objectives: To evaluate the risk of a recurrence of immune toxic effects associated with anti-programmed cell death 1 antibody (anti-PD-1) therapy after discontinuation of ipilimumab monotherapy because of severe AEs., Design, Settings, and Participants: This cohort study conducted at 19 French melanoma referral centers included patients with metastatic melanoma who experienced severe immune-related AEs after ipilimumab therapy and then were treated with anti-PD-1 therapy between February 1, 2013, and December 31, 2016. The study cutoff was June 1, 2017. Statistical analysis was performed from June 1, 2016, to August 31, 2017., Exposures: Monotherapy with at least 1 cycle of ipilimumab that was associated with a grade 3 or 4 immune-related AE and subsequent treatment with at least 1 cycle of an anti-PD-1 (nivolumab or pembrolizumab) therapy., Main Outcomes and Measures: The primary outcome was the rate of immune-related AEs associated with anti-PD-1 therapy. Secondary outcomes were characteristics of ipilimumab-related and anti-PD-1 immune-related AEs and overall response rate and overall survival associated with anti-PD-1 therapy., Results: Of 56 patients with metastatic melanoma included in the study, all of whom experienced severe immune-related AEs after ipilimumab therapy (31 [55%] male; mean [SD] age, 64 [14.9] years), 20 (36%) experienced at least 1 immune-related AE associated with pembrolizumab (6 of 20 [30%]) or nivolumab (14 of 20 [70%]) therapy. A total of 12 patients (21%) experienced grade 3 or 4 immune-related AEs, and among these patients, 4 (33%) presented with the same immune-related AE as with ipilimumab therapy. Severe immune-related AEs were resolved with use of systemic corticosteroids (7 [58%]) and/or anti-tumor necrosis factor (1 [8%]), and no grade 5 toxic effects were reported. Five patients discontinued anti-PD-1 therapy because of immune-related AEs. The overall response rate was 43%, with a median overall survival of 21 months (interquartile range, 18 to ongoing)., Conclusions and Relevance: The findings suggest that anti-PD-1 therapy may be associated with reduced risk of toxic effects and improved survival among patients who have experienced severe toxic effects after ipilimumab therapy.

Background: Targeted therapies such as BRAF and MEK inhibitors and immunotherapies have been made available to treat melanoma., Objectives: To provide an overview of the management of the French Stage III melanoma population after complete lymph node resection prior to new adjuvant therapies., Materials and Methods: A subgroup data analysis., Results: Data from 1,835 patients were analysed (15.58% Stage IIIA, 39.24% Stage IIIB, 43.92% Stage IIIC and 1.25% Stage IIID). Superficial spreading melanoma was the most frequent (70.98% in Stage IIIA for whom mutation analysis was performed; BRAF mutation was identified in up to 62% Stage IIIA patients). Sentinel lymph node biopsy was performed in 88.46% of Stage IIIA patients, 42.36% of Stage IIIB, 53.97% of Stage IIIC and 34.78% of Stage IIID. Up to 80% of Stage IIIA patients had no adjuvant treatment follow-up. Ulceration (p = 0.004; RR: 2.98; 95% CI: 1.4-6.3) and age at diagnosis (p = 0.0002; RR: 1.04; 95% CI: 1.02-1.06) were significant predictive factors for survival. Adjuvant interferon-α was administered in up to 13.04% of Stage IIID patients., Conclusion: Only a small number of Stage III melanoma patients were treated with interferon-α in adjuvant settings. New adjuvant therapies are currently having an effect on clinical practice in France, increasing survival and decreasing cost.