Immune-related adverse events and immune checkpoint inhibitor tolerance on rechallenge in patients with irAEs: a single-center experience

Abstract

Background: Given the widespread use of immune checkpoint inhibitors (ICIs), newer immune related adverse events (irAEs) have come to light, including flare-ups of preexisting autoimmune disorders (AIDs) and delayed immune-related events. We aimed to identify the frequency and severity of new IRAEs, including AID flares in cancer patients treated with ICIs at our institution. We also studied the tolerability of ICIs upon rechallenge in patients with irAEs and hospital admissions due to irAEs in a community setting in rural Maine.

Methods: We conducted a retrospective chart review analysis of all patients with cancer who received anti-PDL1/PDL1 inhibitors nivolumab, pembrolizumab, atezolizumab, and durvalumab at our tertiary care center from November 2015 to March 2019. Demographic data, cancer type and stage, irAEs, hospital admissions due to irAEs, and drug treatment information was extracted.

Results: We included 465 patients who received ICIs, 115 (out of 465 25%) developed new irAEs. Preexisting AID were identified in 47 (out of 465) (10%), AID flares were observed in 12 patients (25% of 47). 17 (out of 47 36%) were on immunosuppression for underlying AID, 5 (out of 17, 29%) developed flares. Overall, 148 (32% of 465) irAEs occurred, as some patients had multiple toxicities. Majority were treated for Lung cancer (63%), followed by melanoma and genitourinary cancers. Due to irAE severity, treatment was permanently discontinued in 15% (out of 465) patients. Hospital admissions due to irAEs were required for 34 patients (7.3% of 465). ICI rechallenge was performed in 27 patients (6% of 465), and majority tolerated well.

Conclusion: Our study shows that ICIs were generally well tolerated and can be used safely even in patients with preexisting AIDs; it is encouraging to see majority tolerated rechallenge with ICIs well.

Keywords: Anti-PD1/PDL1 inhibitors; Delayed immune-related events; Hospital admissions due to irAEs; Immune checkpoint inhibitors; Immune-related adverse events; Preexisting autoimmune disorders; Rechallenge with ICIs.