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

• Published in: Frontiers in immunology Vol. 12; p. 730320
• Main Authors: Zhao, Qing, Zhang, Jianwei, Xu, Lingyi, Yang, Huaxia, Liang, Naixin, Zhang, Li, Zhang, Fengchun, Zhang, Xuan
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 27.09.2021
• Subjects: cancer; Drug-Related Side Effects and Adverse Reactions - diagnosis; Drug-Related Side Effects and Adverse Reactions - epidemiology; Drug-Related Side Effects and Adverse Reactions - immunology; efficacy; Humans; immune checkpoint inhibitors; Immune Checkpoint Inhibitors - administration & dosage; Immune Checkpoint Inhibitors - adverse effects; immune-related adverse events; Immunology; Incidence; Neoplasms - drug therapy; Neoplasms - immunology; rechallenge; Retreatment; Risk Assessment; Risk Factors; safety; Severity of Illness Index; Treatment Outcome; cancer; immune checkpoint inhibitors; rechallenge; safety; efficacy; immune-related adverse events
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2021.730320

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. 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. 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; < 0.0001), but similar incidence for high-grade irAEs ( > 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 ( < 0.05), whereas initial anti-PD-1/PD-L1 antibodies were associated with a lower recurrence ( < 0.05). Anti-PD-1/PD-L1 antibodies rechallenge was associated with a lower all-grade irAE recurrence ( < 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 ( > 0.05). ICI rechallenge after irAEs showed lower safety and similar efficacy outcomes compared with initial ICI treatment. PROSPERO, identifier CRD42020191405.