Immune checkpoint inhibitor use and tuberculosis: a systematic review of the literature

Abstract

Background

An amassing body of evidence exists to support an association between the use of immune checkpoint inhibitors (ICIs) and the development of tuberculosis (TB).

Methods

We performed a systematic review of the literature to assess the nature of this relationship using PubMed, EMBASE and meeting proceedings.

Results

We have identified 16 patients who developed active TB during immunotherapy. Median age was 61 (range: 49–87). Twelve (75%) were male and 4 (25%) were female. Lung cancer was the most common type of cancer (n = 8), followed by melanoma (n = 3) and head and neck cancer (n = 3). Median time to TB reactivation after initiation of ICI therapy was 6.3 months (range: 1–24 months). Two (13%) patients died of complications of TB (spinal cord compression, GI perforation). TB reactivation in organs (pericardium, bone, liver, and GI track; one each) other than the lungs has been documented. We did not find any cases of TB reactivation that occurred during anti–CTLA-4 therapy.

Conclusion

Findings from our systematic review indicate that PD-(L)1 inhibitors are linked to TB reactivation. TB activation can occur in various organs and TB-related fatalities have been reported. TB screening before starting immunotherapy should be considered in high-risk patient populations. Further research, including prospective studies with patients whose baseline TB status is known, is necessary to better understand the incidence of TB reactivation during ICI therapy and how best to manage TB that develops during immunotherapy.