Incidence of pneumonitis with CTLA-4 inhibitors in non-small cell lung cancer: a systematic review and meta-analysis.

BACKGROUND

CTLA-4 inhibitors, such as tremelimumab and ipilimumab, are increasingly used in the treatment of non-small cell lung cancer (NSCLC). This meta-analysis aims to evaluate the incidence of pneumonitis associated with these inhibitors and explore potential differences between individual agents.

METHODS

A systematic search across three online databases identified 911 records. After screening for duplicates and irrelevant articles, nine studies with a total of 4,164 patients were included. Risk of bias was assessed using the Cochrane "Risk of Bias" tool. Pneumonitis incidence was analyzed using a random-effects model.

RESULTS

The overall incidence of any-grade pneumonitis was 4.0% [95% CI (2.2%, 5.8%)]. High-grade pneumonitis occurred in 1.6% [95% CI (0.5%, 2.6%)]. Subgroup analysis revealed that tremelimumab was associated with a higher incidence of both any-grade (8.0% vs. 2.0%) and high-grade (3.0% vs. 1.0%) pneumonitis compared to ipilimumab. In a comparison with a control group, patients receiving CTLA-4 inhibitors had a significantly higher incidence of any-grade pneumonitis [OR = 3.00, 95% CI (1.60, 5.64), < 0.01]. However, the difference in high-grade pneumonitis between the two groups was not statistically significant [RR = 1.79, 95% CI (0.83, 3.85), = 0.14].

CONCLUSION

This meta-analysis indicates that CTLA-4 inhibitors are associated with a higher incidence of pneumonitis in NSCLC patients, particularly with tremelimumab. These findings underline the importance of close monitoring for pneumonitis in patients receiving CTLA-4 inhibitors, especially tremelimumab, and suggest the need for further research into prevention and management strategies.