The Incidence And Risk Factors Of Pneumonitis In Patients Treated With Immune Checkpoint Inhibitors

Purpose:We conducted a meta-analysis of published clinical trials to determine the relationship between the risks of pneumonitis and pneumonitis-related death and programmed cell death-1(PD-1)inhibitor treatment in patients with cancer.Materials and methods:We examined clinical trials from the Medline and Google Scholar databases.Data from original studies and review articles were also cross-referenced and evaluated.Randomized Phase II and Phase III trials of pembrolizumab and nivolumab treatment in patients with cancer were eligible for the analysis.Information about the participants,all grade and high-grade pneumonitis,and pneumonitis-related death was extracted from each study and analyzed.Results:After the exclusion of ineligible studies,12 clinical trials were included in the analysis.The odds ratio(OR)for all-grade pneumonitis after PD-1 inhibitor treatment was 4.59(95%confidence interval[CI]:2.51-8.37;P 0.00001),and the OR for high-grade pneumonitis after PD-1 inhibitor treatment was 3.83(95%CI:1.54-9.48;P 0.004).The OR for pneumonitis related death after PD-1 inhibitor treatment was 2.47(95%CI:0.41-14.81;P 0.32).Moreover,the OR for all-grade pneumonitis after nivolumab/ipilimumab combination therapy versus nivolumab monotherapy was 3.54(95%CI:1.52-8.23;P 0.003),and that for high-grade pneumonitis after nivolumab/ipilimumab combination therapy versus nivolumab monotherapy was 2.35(95%Cl:0.45-12.13;P 0.31).Treated cancer appeared to have no effect on the risk of pneumonitis.Conclusion:Our data showed that PD-1 inhibitors were associated with increased risks of all-grade and high-grade pneumonitis compared with chemotherapy or placebo controls in patients with cancer.However,we noted no significant difference between patients treated with a PD-1 inhibitor and patients treated with control regimens with respect to the risk of pneumonitis-related death.Purpose:Pneumonitis is an uncommon but potentially fatal toxicity of anti-programmed death-1(PD-1)monoclonal antibodies(mAbs),but its clinical features and risk factors are poorly studied.We aimed to explore the clinical features,management,outcomes and risk factors for pneumonitis related with anti-PD-lmAbs in real-world.Methods:We conducted this case-control study to explore the risk of pneumonitis in patients with advanced cancer who underwent anti-PD-1 mAbs therapies.55 patients who developed pneumonitis(cases)and 110 patients who didn't(controls)were matched using a propensity-score matching algorithm that accounted for confounding effects of baseline characteristics.We described the characteristics and clinical outcome of pneumonitis induced by anti-PD-lmAbs and calculated odds ratios for the association of pneumonitis with selected risk factors.Results:The median time to onset of pneumonitis was 85 days with a range from 2 to 277 days.85.7%of who treated with steroid therapy(12 of 14)were resolved/improved.Three patients experienced recurrent pneumonitis.Significant risk factors for pneumonitis related with anti-PD-lmAbs were:male sex,a history of prior thoracic radiotherapy,combination therapy and underlying lung condition with odds ratios of 3.23(1.39-7.51),3.97(1.75-9.04),2.62(1.35-5.10)and 2.76(1.40-5.43),respectively.In the multivariate logistic regression analysis,male sex,a history of prior thoracic radiotherapy,combination therapy and underlying lung condition were associated with the incidence of pneumonitis.Conclusions:Pneumonitis associated with anti-PD-1 mAbs is a serious adverse effect in the clinical setting that cannot be ignored.Most events are low grade and improve/resolve with drug holding/steroid.Patients of male sex,history of prior thoracic radiotherapy,combination therapy and underlying lung condition need more attention for pneumonitis.