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

INTRODUCTION

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.

METHODS

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).

RESULTS

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.

CONCLUSION

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.