Pneumonitis in immunotherapy alone vs. chemoimmunotherapy: A systematic review and meta-analysis.

Abstract

e21120 Background: Immune checkpoint inhibitors (ICIs) are commonly used in the treatment of non-small cell lung cancer (NSCLC), and are given alone or in combination with cytotoxic chemotherapy. These agents are sometimes associated with immune related adverse events (irAEs). Pneumonitis in particular is a common and sometimes life-threatening complication of treatment with ICIs, especially in lung cancer patients. Chemotherapy is known to cause immune suppression and deplete T cell populations, and might be expected to attenuate the incidence or severity of irAEs when given with ICIs. To date, few studies explore this possibility. This meta-analysis compared the incidence of any grade and severe (grade ≥3) pneumonitis in patients who received ICIs alone vs. combination ICI + chemotherapy for the treatment of advanced NSCLC. Methods: Embase and PubMed databases were searched through May 2021 for clinical trials investigating the use of ICIs for treatment of advanced NSCLC alone and/or in combination with chemotherapy. Interventions were categorized into ICI alone vs. ICI + chemotherapy and rates of any grade and severe (grade ≥3) pneumonitis for patients in each category were collected. The incidence of these events across interventions was aggregated using inverse variance weighting, and rates among patients who received ICI alone and ICI + chemotherapy were compared. Results: 1929 studies were identified by the initial search, of which 36 met inclusion criteria. From these, 24 interventional arms using ICIs alone (total patients n = 11,163) and 12 using combination therapy (n = 4,129) were identified and analyzed. ICIs included agents targeting PD1 (n = 22), PD-L1 (n = 11), CTLA-4 (n = 1), and the combination of CTLA-4 with PD1 or PD-L1 (n = 2). Rates of any grade pneumonitis did not differ significantly between patients who received ICI alone vs combination therapy (0.03; 95% CI 0.02-0.04 vs 0.04; 95% CI 0.02-0.08; P = 0.5). Rates of severe pneumonitis also did not differ between groups (0.01; 95% CI 0.01-0.02 vs 0.01; 95% CI 0.00 – 0.02; P = 0.5). Conclusions: No difference was found in the rates of any grade or severe pneumonitis between patients who received ICI alone vs. ICI + chemotherapy.