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Introduction  Little evidence exists on the safety and efficacy of the rechallenge of immune checkpoint inhibitors (ICIs) after immune-related adverse events (irAEs) in patients with cancer.    Methods  We searched PubMed, Web of Science, Embase, and Cochrane for articles on ICI rechallenge after irAEs for systemic review and meta-analysis. The outcomes included the incidence and associated factors for safety and objective response rate (ORR) and disease control rate (DCR) for efficacy.    Results  A total of 789 ICI rechallenge cases from 18 cohort studies, 5 case series studies, and 54 case reports were included. The pooled incidence of all-grade and high-grade irAEs after rechallenge in patients with cancer was 34.2% and 11.7%, respectively. Compared with initial ICI treatment, rechallenge showed a higher incidence for all-grade irAEs (OR, 3.81; 95% CI, 2.15–6.74;  p  < 0.0001), but similar incidence for high-grade irAEs ( p  > 0.05). Types of initial irAEs (pneumonitis and global irAEs) and cancer (non-small cell lung cancer and multiple cancer) recapitulated these findings. Gastrointestinal irAEs and time interval between initial irAEs and ICI rechallenge were associated with higher recurrence of high-grade irAEs ( p  < 0.05), whereas initial anti-PD-1/PD-L1 antibodies were associated with a lower recurrence ( p  < 0.05). Anti-PD-1/PD-L1 antibodies rechallenge was associated with a lower all-grade irAE recurrence ( p  < 0.05). The pooled ORR and DCR after rechallenge were 43.1% and 71.9%, respectively, showing no significant difference compared with initial ICI treatment ( p  > 0.05).    Conclusions  ICI rechallenge after irAEs showed lower safety and similar efficacy outcomes compared with initial ICI treatment.    Systematic Review Registration  PROSPERO, identifier CRD42020191405.

frontiers in immunology

Safety and Efficacy of the Rechallenge of Immune Checkpoint Inhibitors After Immune-Related Adverse Events in Patients With Cancer: A Systemic Review and Meta-Analysis