PD-1/L1 inhibitors may increase the risk of pericardial disease in non-small-cell lung cancer patients: a meta-analysis and systematic review

Immunotherapy. 2022 May;14(7):577-592. doi: 10.2217/imt-2021-0223. Epub 2022 Apr 4.

Abstract

Background: The advent of PD-1/L1 inhibitors has changed the landscape for patients with non-small-cell lung cancer (NSCLC). Meanwhile, the adverse events of PD-1/L1 inhibitors have been focused. Methods: The Cochrane Central Register of Controlled Trials, PubMed and Embase databases and ClinicalTrials.gov were searched from inception to February 2021. Results: 18 studies involving 11,394 patients with NSCLC were included. PD-1/L1 inhibitor monotherapy was associated (relative risk, 95% confidence interval) with an increased risk of pericardial effusion (2.72 [1.45-5.12]; p = 0.002) and cardiac tamponade (2.76 [1.15-6.62]; p = 0.023), whereas PD-1/L1 inhibitors combined with chemotherapy did not increase the risk of pericardial effusion and cardiac tamponade (3.08 [0.93-10.21]; p = 0.066 and 3.27 [0.37-28.94]; p = 0.288, respectively). Conclusion: For patients with NSCLC, treatment with PD-1/L1 inhibitor monotherapy increases the risk of pericardial effusion and cardiac tamponade, but PD-1/L1 inhibitors combined with chemotherapy do not.

Keywords: PD-1/L1 inhibitors; adverse events; cardiac tamponade; chemotherapy; meta-analysis; non-small-cell lung cancer; pericardial effusion.

Plain language summary

In this study, the authors found that the incidence of pericardial effusion and cardiac tamponade in non-small-cell lung cancer patients treated with PD-1/L1 inhibitors was 0.63% and 0.35%, respectively, and in chemotherapy was 0.07% and less than 0.01%, respectively. The authors found that PD-1/L1 inhibitors combined with chemotherapy did not increase the risk of cardiac adverse events (AEs); however, the risk of cardiac AEs with PD-1/L1 inhibitor monotherapy should be considered, and the damage of pembrolizumab to the pericardium needs further attention. The mechanism of pericardial effusion and cardiac tamponade is not well understood, and pseudoprogression cannot be ruled out. Although the incidence of cardiac AEs is low, the prevention and management of immunotherapy should be paid attention to.

Publication types

  • Meta-Analysis
  • Review
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • B7-H1 Antigen
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Cardiac Tamponade* / drug therapy
  • Cardiac Tamponade* / epidemiology
  • Humans
  • Immune Checkpoint Inhibitors / adverse effects
  • Lung Neoplasms* / drug therapy
  • Pericardial Effusion* / drug therapy
  • Pericardial Effusion* / epidemiology
  • Programmed Cell Death 1 Receptor / therapeutic use

Substances

  • B7-H1 Antigen
  • Immune Checkpoint Inhibitors
  • Programmed Cell Death 1 Receptor