OBJECTIVES

: PD-1 inhibitors have emerged as a front-line treatment for several types of cancer based on their ability to support the immune system in attacking and shrinking tumors. However, PD-1 inhibitor therapies are known to be associated with irAEs. The study evaluated irAEs reported in different organ classes by melanoma patients treated with PD-1 inhibitor therapies.

METHODS

: The study was carried out using FAERS database in melanoma patients and limited to the period January 2015 to September 2020. The study considered those AEs which were equal or more prevalent in PD-1/PD-L1 inhibitors as compared to other oncology drugs. From the shortlisted AEs, the irAEs were identified using MedDRA preferred terms and were classified in different organ classes including endocrine, cardio-vascular, digestive, musculo-skeletal, nervous-system and skin. Disproportionality analysis with reporting odds ratios (ROR) and 95% confidence intervals (95% CI) were used to estimate the irAEs reported in these organ classes.

RESULTS

: Out of 28,335 adverse events reported in melanoma patients, 1,985 (7.0%) were identified as irAEs of interest. Of these irAEs, PD-1 inhibitor therapies were the primary suspect in 1,413 (71.2%) cases. The patients involved in these cases were more males (54%) than females (39%), and with mean age of 64.7 years. The analysis showed that PD-1 inhibitor therapies had disproportionality signals and were potentially associated with irAEs as compared to non-PD-1 treated patients (ROR: 4.37; 95% CI: 3.95-4.83). Among organ classes, ROR for irAEs affecting the eye (27.13; 95% CI: 3.61-203.90) was the highest, followed by musculoskeletal system (7.25; 95% CI: 5.12-10.27) and Systemic/ Multi-organ/Non-specific (6.38; 95% CI: 4.91-8.29). Relatively smaller ROR was observed in GI and liver organs.

CONCLUSIONS

: The current analysis identified the disproportionality signals of irAEs in melanoma patients treated with PD-1 inhibitor therapies as compared to non-PD-1 inhibitor treatments.