Safety of Immunotherapy Rechallenge After Immune-related Adverse Events in Patients With Advanced Cancer

This retrospective study aimed to investigate the safety profile of continuing or rechallenging patients with advanced cancer who developed grade≥2 immune-related adverse events (irAEs) on immunotherapy-based regimens. Our study had 25, 20, and 40 patients (N=85) in the Treatment Continuation (TCG), Non-Rechallenge (NRG), and Rechallenge Groups (RG), respectively. Subsequent irAEs recurrence were more common in RG than TCG and NRG (78% vs. 56% vs. 25%, P <0.001). The same subsequent irAEs recurrences occurred on 42% of RG, 4% of TCG, and 15% of NRG ( P <0.001). On the RG, there was a nonstatistical trend of shortening interval time between time from treatment rechallenge to subsequent irAEs when compared with time from first treatment to initial grade≥2 irAEs (5.86 vs. 8.86 wk, P =0.114). Patients who had cardiac irAEs were not rechallenged. Several high-risk features were identified to prognosticate risk of irAEs recurrences upon treatment rechallenge, including age 65 years and above ( P =0.007), programmed cell death protein 1 inhibitors ( P <0.001), grade 3 irAEs ( P =0.003), pneumonitis type ( P =0.048), any systemic corticosteroid use ( P =0.001)/high-dose systemic corticosteroid use ( P =0.007)/prolonged ≥4-week corticosteroid use ( P =0.001) for irAEs management, and early development of irAEs ( P =0.003). Our study concluded that it was relatively safe to continue or rechallenge patients with advanced cancers on immunotherapy-based regimens postdevelopment of certain grade≥2 irAEs, except for cardiac, neurological, or any grade 4 irAEs. Subsequent irAEs were common, no more severe, involved the same organ sites, and occurred more quickly than the original irAE. Close monitoring of all potential irAEs is required when rechallenging a patient on immunotherapy, especially for patients with high-risk features.