Patterns of immune-related adverse events (irAEs) in adolescent and young adult (AYA) patients with melanoma receiving immune checkpoint inhibitors (ICIs).

12117 Background: ICIs are increasingly used in AYAs with cancer, however, limited data exists on the frequency and pattern of irAEs in this population and the ability to rechallenge with ICIs after irAEs. Methods: This retrospective study analyzed AYAs aged 15-39 with melanoma who received treatment with ICIs at MD Anderson Cancer Center from 2013 to 2023. Treatment cessation was defined as switching therapies or pausing the original treatment for over 3 months, and rechallenge as resuming immunotherapy post-cessation. Results: A total of 136 pts were included, 80 were male (59%), with median age at 33 years (range, 15-39 years) upon initial ICI exposure. The majority had non-acral cutaneous melanoma (107, 79%) and 83 (63%) had a BRAF V600E/R/K alteration. Ninety-three percent patients had stage III/IV cancer at ICI treatment initiation. Targeted therapy was used in 20 patients (15%) prior to starting ICI and 16 patients (12%) concurrently. Combination immunotherapy was utilized in 43% of cases, while monotherapy in 57%. The initial intent for ICIs was adjuvant in 51% of the cases, palliative in 37% and neoadjuvant in 12%. The incidence of any-grade and grade III/IV irAEs with 1st line ICI therapy was 60% and 21% for the full cohort (with combination of CTLA-4/PD-1 blockers 70% and 33%; with PD-1 blockers monotherapy was 50% and 9%, respectively). Forty-eight AYAs had multi-system irAEs (35%) and 23 were grade III/IV. Thirty-two (24%) patients had their initial ICI stopped due to irAEs with hepatitis (31%, 10/32) and colitis (28%, 9/32) being the most common causes. Eighteen patients (13%) had irAE-related hospitalizations. Specific irAEs are listed in the table. Seventy-two (53%) patients were rechallenged with ICIs. Of these, 51 had previous irAEs and among these, 71% had recurrent irAEs. Seventy-six percent (36/51) experienced irAEs again with 33% (17/51) having the same irAEs. Twenty-six percent of patients (13/51) had grade III/IV irAEs. Conclusions: In AYAs with melanoma who were treated with ICIs, irAE is one of the major reasons for treatment interruption. The incidence of irAEs in AYAs appears somewhat lower than the rates previously reported in registrational trials, though this should be interpreted with caution given retrospective nature of current study. Patients with prior irAEs have a higher risk of recurrent or new irAEs upon rechallenge, however, the majority were low grade without serious negative outcome. Table: see text