Immune-related adverse events in a nationwide cohort of real-world melanoma patients treated with adjuvant anti-PD1 - Seasonal variation and association with outcome.

Immune checkpoint inhibitors (ICIs) carry the risk of immune-related adverse events (irAEs), a significant concern as therapy has transitioned to the adjuvant setting. Balancing therapeutic benefits against potential risks is crucial, necessitating real-world data from an unselected patient population in addition to clinical trial data to ensure optimal clinical decision-making. This nationwide real-world study assessed irAEs in patients receiving adjuvant anti-PD1 therapy, primarily nivolumab, for resected stage III-IV melanoma between 2018-2022. Data were retrieved from two national databases: the IMMUNOTOX database and the Danish Metastatic Melanoma Database (DAMMED). IrAEs were sub-grouped according to organ systems graded using CTCAE ver. 5.0 ranging from mild toxicities (grade 1-2) to severe (grade 3-4) and fatal (grade 5). Among 792 included patients, (55 % male, median age 62 years (range 16-88)), 697 patients (88 %) experienced an irAE. Severe irAEs occurred in 116 patients (15 %) and five (0.6 %) died due to toxicity. A landmark analysis showed that patients who experienced at least one irAE before the 1st evaluation at 90 days had an increased progression free survival (PFS) (p = 0.032) and overall survival (OS) (p = 0.0071). Additionally, a seasonal pattern was noted with higher incidence of irAEs during summer. The prevalence of irAEs in real-world patients is comparable to the observed risk in clinical trials. Patients experiencing irAEs demonstrate a lower risk of melanoma relapse. Further, gender, age and seasonal variation may impact the incidence of irAEs.

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Déclaration de conflit d'intérêts

Declaration of Competing Interest Within the last two years: RSJ received travel/conference expenses from Pierre Fabre. LMG has received honoraria for lectures from BMS and from MSD for travel and conference support. MD has received proprietary data access from Bristol Myers Squibb and Genentech and is an advisor of Achilles Therapeutics. CAH has received honoraria for lectures from BMS, AstraZeneca and GSK and consultancies for AstraZeneca. HSC has received research grant from MSD. CHR reports grants from Novo Nordisk Foundation and Helsinn Healthcare SA, and personal fees from Bristol-Myers Squibb, Helsinn Healthcare SA, Pharmanovia, and Astellas Pharma outside the submitted work. IMS has received honoraria for consultancies and lectures from IO Biotech, Novartis, MSD, Pierre Fabre, BMS, Novo Nordisk, TILT Bio; research grants from IO Biotech, BMS, Lytix, Adaptimmune, TILT Bio. EE received honoraria from BMS, Pierre Fabre, Novartis, and MSD for consultancies and lectures, and from MSD and Pierre Fabre for travel and conference support. MD has received honoraria for lectures from Roche (past 2 years) and received access to research data from Bristol Myers Squibb and from Genentech. All other authors declare that they have no conflicts of interest.