Immune-Related Adverse Events (irAE) in Cancer Immune Checkpoint Inhibitors (ICI) and Survival Outcomes Correlation: To Rechallenge or Not?

SIMPLE SUMMARY: This study examined the real-world experience and occurrence of immune-related adverse events (irAEs) under cancer checkpoint immunotherapy, and the relationship between its treatment rechallenge status and their impact on clinical outcomes. The current study demonstrates that immune checkpoint inhibitors (ICI) reinitiation after an irAE-related interruption in the setting of cancer immunotherapy was not associated with significantly improved survival outcome when compared with those without ICI treatment reinitiation after irAE-related therapy interruption. ABSTRACT: Introduction: There is growing recognition of immune related adverse events (irAEs) from immune checkpoint therapies being correlated with treatment outcomes in certain malignancies. There are currently limited data or consensus to guide management of irAEs with regards to treatment rechallenge. Methods: We conducted a retrospective analysis with an IRB-approved protocol of adult patients seen at the WVU Cancer Institute between 2011–2019 with a histopathologic diagnosis of active cancers and were treated with immune checkpoint inhibitors (ICI) therapy. Results: Demographics were similar between the ICI interrupted irAE groups within cancer types. Overall, out of 548 patients who received ICI reviewed, there were 133 cases of ≥1 irAE found of any grade. Being treated with anti-CTLA-4 inhibitor ICI was associated with lower risk of death compared to anti-PD-1 ICI. The overall survival difference observed for irAE positive patients, between rechallenged (37.8 months, reinitiated with/without interruption; 38.6 months, reinitiated after interruption) and interrupted/non-reinitiated (i.e., discontinued) groups (24.9 months) was not statistically significant, with a numerical trend favoring the former. Conclusions: Our exploratory study did not identify significantly different survival outcomes among the Appalachian West Virginia adult cancer patients treated with ICI who developed irAE and had treatment reinitiated after interruption, when compared with those not reinitiated.