AUTHOR=Zhao Qing , Zhang Jianwei , Xu Lingyi , Yang Huaxia , Liang Naixin , Zhang Li , Zhang Fengchun , Zhang Xuan 

TITLE=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

JOURNAL=Frontiers in Immunology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.730320

DOI=10.3389/fimmu.2021.730320

ISSN=1664-3224

ABSTRACT=<sec><title>Introduction</title><p>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.</p></sec><sec><title>Methods</title><p>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.</p></sec><sec><title>Results</title><p>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; <italic>p</italic> &lt; 0.0001), but similar incidence for high-grade irAEs (<italic>p</italic> &gt; 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 (<italic>p</italic> &lt; 0.05), whereas initial anti-PD-1/PD-L1 antibodies were associated with a lower recurrence (<italic>p</italic> &lt; 0.05). Anti-PD-1/PD-L1 antibodies rechallenge was associated with a lower all-grade irAE recurrence (<italic>p</italic> &lt; 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 (<italic>p</italic> &gt; 0.05).</p></sec><sec><title>Conclusions</title><p>ICI rechallenge after irAEs showed lower safety and similar efficacy outcomes compared with initial ICI treatment.</p></sec><sec><title>Systematic Review Registration</title><p>PROSPERO, identifier CRD42020191405.</p></sec>