(C-211) Immune-mediated adverse events in patients with high-risk melanoma receiving immune checkpoint inhibitors in adjuvant and first-line treatment settings: a real-world analysis

Background: Immune checkpoint inhibitors (ICIs) are the standard of care in adjuvant and first-line (1L) settings of high-risk melanoma. Evidence from clinical trials has shown a burden of immune-mediated adverse events (imAEs) resulting in treatment discontinuation in ICI-treated cancer patients, but real-world data on imAEs in high-risk patients is limited.

Objectives: The primary objective is to describe the incidence of imAEs resulting in therapy discontinuation among real-world patients with high-risk melanoma (stage IIIB-IV) receiving ICIs in adjuvant and 1L settings. The incidence of overall imAEs was examined as a secondary objective.

Methods: This is a retrospective cohort study among U.S. adult patients with high-risk melanoma treated with ICIs (1/1/2016-7/24/2023) in the ConcertAI Patient360 database. Two cohorts were identified: patients receiving adjuvant ICI treatment post-surgery and those receiving 1L ICIs. Eligible ICI regimens included 1) ipilimumab and nivolumab, 2) nivolumab and relatlimab, 3) nivolumab, or 4) pembrolizumab. Patients were followed from the start of the regimen until the earliest of: incident imAE resulting in discontinuation, death, initiation of a new line of therapy (LOT), 90 days after end of LOT, last follow-up, or 7/31/2023.

Results: Patients in the adjuvant (N=252) and 1L (N=995) cohorts had median ages of 63.7 (IQR=54.4-71.9) and 68.4 (59.7-76.9) years, respectively, and were primarily male (66.3% and 66.1%) and White (92.5% and 93.0%). The most common ICI regimens were nivolumab (77%) in the adjuvant cohort, and combined ipilimumab and nivolumab (38%) in the 1L cohort. ImAEs associated with therapy discontinuation occurred in 5.6% of adjuvant ICI-treated patients and 7.5% of 1L patients. The 12-month A-J estimates of cumulative incidence for imAEs were 5.3% (95% confidence interval [CI]: 3.0%, 8.6%) and 7.1% (5.6%, 8.9%) in the adjuvant and 1L cohorts, respectively. Incidence rates were 0.5 (0.27, 0.83) and 0.62 (0.49, 0.78) per 100 person-months in the adjuvant and 1L cohorts, respectively. Overall imAEs were also more frequent in 1L-treated patients compared with adjuvant ICIs (12-month cumulative incidence: 15% vs. 7.3%). When stratified by ICI regimen, imAEs associated with discontinuation occurred most in 1L patients receiving ipilimumab plus nivolumab.

Conclusions: This real-world analysis indicated that imAEs associated with drug discontinuation are somewhat common in patients with high-risk melanoma receiving ICIs in both adjuvant and 1L settings, usually occurring within the first few months of treatment. Lastly, patients treated with 1L ICIs tended to have earlier and greater rates of imAEs compared with adjuvant ICIs.