Immune Checkpoint Inhibitor Rechallenge After Immune-Related Adverse Events: A Systematic Review and Meta-Analysis.
Xinwei Chen, Shun Gao, Xialin Zhang et al.
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In 30 seconds
This systematic review and meta-analysis pooled observational cohort evidence on restarting immune checkpoint inhibitors (ICIs) after treatment interruption for an immune-related adverse event (irAE). Across 35 cohorts comprising 1551 rechallenged patients, index-irAE recurrence was 25.4% (95% confidence interval [CI], 21.4-29.7). Any post-rechallenge irAE, including new events, occurred in 44.2% (95% CI, 37.8-50.8), while pooled objective response and disease control were 44.3% and 72.7%, respectively. The findings indicate that toxicity is common after resumption, alongside evidence of antitumor activity.
Key findings
- Index-irAE recurrence after rechallenge was 25.4% (95% confidence interval [CI], 21.4-29.7; 30 studies).
- Any post-rechallenge irAE, recurrent or new, occurred in 44.2% (95% CI, 37.8-50.8; 23 studies).
- Grade ≥ 3 post-rechallenge irAE, recurrent or new, occurred in 19.8% (95% CI, 15.3-25.1; 22 studies).
- Pooled objective response and disease control were 44.3% and 72.7%, respectively.
Why it matters
The pooled estimates quantify both the potential for antitumor activity and the substantial risk of further toxicity when ICIs are resumed after an irAE. This supports careful, individualized risk-benefit assessment rather than assuming rechallenge is either uniformly unsafe or reliably beneficial. The review also highlights irAE phenotype, recovery status, and rechallenge strategy as areas needing prospective evaluation.
What to keep in mind
The evidence came from observational cohorts, and endpoint-specific denominators varied. Survival data were limited, and no summary hazard ratio was calculated.