Immune Checkpoint Inhibitors and Tuberculosis Infection in Lung Cancer: A Case Series and Systematic Review With Pooled Analysis

The association between immune checkpoint inhibitors (ICIs) and tuberculosis (TB) infection in patients with lung cancer remains largely elusive. We performed a systematic review and conducted a retrospective analysis of TB infection in patients with lung cancer and ICI exposure to assess the clinical characteristics and outcomes using PubMed, EMBASE, and the Cochrane Library. The time interval from ICI administration to diagnosis of TB between patients with and without a history of TB was compared using Kaplan-Meier analysis. A multivariate Cox regression model was used to identify potential risk factors associated with the time interval of TB development. Twenty-four studies including 53 patients with lung cancer were included. The median age of the patients was 64 years. Eight patients had a history of TB. The median time interval from ICI administration to TB diagnosis was 3 months. In retrospective analysis, 5 (1.16%, 95%CI 0.38% to 2.68%) patients with lung cancer developed TB during ICI treatment. The median time interval was 10.4 months. In a pooled analysis, the median time interval in the without-TB and with-TB groups was 7.00 and 2.35 months, respectively (P = .034). Multivariate Cox regression analyses revealed a history of TB to be an independent factor affecting the time interval of TB activation in patients with lung cancer and ICI exposure (HR 3.59; 95%CI 1.17 to 11.02; P = .026). Therefore, TB infection should be considered in patients with lung cancer during or after ICI treatment. Moreover, we found TB history to be a positive risk factor for a shorter median time interval from ICI to TB diagnosis in patients with lung cancer receiving ICI.