Patterns of immune-related adverse events and treatment responses in adolescents and young adults with melanoma during initial and rechallenge immune checkpoint inhibitor therapy.
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BACKGROUND: Immune checkpoint inhibitors (ICIs) are increasingly used in adolescents and young adults (AYAs) with cancer; however, data on treatment response, the frequency and pattern of immune-related adverse events (irAEs), and the feasibility of ICI rechallenge after irAEs are limited. METHODS: This retrospective study included 136 AYAs (80 males and 56 females) who received ICI therapy for melanoma at our institution from 2013 to 2023. We documented the initial ICI treatment and ICI rechallenge, along with associated irAEs and treatment responses. Kaplan-Meier plots were used to analyze overall survival (OS) and progression-free survival. RESULTS: At ICI initiation, the median age was 33 (range, 15-39) years, and most patients had stage III or IV disease (93%) and BRAF mutations (63%). Treatment settings included adjuvant (n=70), palliative (n=50), and neoadjuvant (n=16). Compared with those receiving ICI monotherapy (n=77), patients receiving ICI combination therapy (n=59) had significantly higher rates of irAEs of any grade (53% vs 75%, p=0.011) and grade three or four irAEs (12% vs 32%, p=0.003) and higher rates of treatment delay (26% vs 51%, p=0.044), and hospitalization (8% vs 20%, p=0.032). ICI rechallenge was common (n=71), even after prior irAEs (n=48). Colitis and hepatitis were the most common irAEs following initial ICI therapy (26% and 23%, respectively) and ICI rechallenge (31% and 29%, respectively). The adjuvant, palliative, and neoadjuvant ICI therapy groups had 5-year OS rates of 86%, 77%, and 88%, respectively. In the palliative therapy group, the overall response rate and disease control rate were 38% and 42% during initial ICI therapy and 35% and 44% during ICI rechallenge. Elevated baseline lactate dehydrogenase levels were associated with worse OS (adjusted HR, 21.04, 95% CI, 1.35 to 328.29, p=0.030), and colitis and/or hepatitis were strongly associated with better OS (adjusted HR, 0.10, 95% CI 0.01 to 0.83, p=0.033). CONCLUSIONS: AYA patients receiving ICI therapy for melanoma had high incidence of colitis and hepatitis and favorable survival. Initial and rechallenge ICI therapy had similar patterns of irAE severity and efficacy. Colitis and hepatitis were associated with improved OS.