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

Abstract

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.

Recurrent choriocarcinoma complicated with leprosy during chemotherapy: A case report and literature review

“…However, when treating cancer patients who also suffer from infections, the use of immunotherapy should be approached with caution. Recently, several cases of TB infection activation in cancer patients receiving ICIs treatment have been reported, [19][20][21][22][23] According to a meta-analysis, the incidence of TB was 35 times higher in PD-1/PD-L1 blockade-treated patients than in the general population. [24] Meanwhile, another observational study revealed that among patients with cancer, the incidence of TB in the group exposed to ICIs was 675.8 per 100,000 person-years (95% confidence interval: 412.8-1043.8), while in the non-exposure group, it was 599.1 per 100,000 person-years (95% confidence interval: 560.5-639.6).…”

Fever of unknown origin associated with immune checkpoint inhibitors

“…Patients undergoing ICIs administration are eight times more likely to contract TB than the general population, according to an observational study ( 49 ). A Meta-analysis revealed that patients receiving PD-1/PD-L1 in developed Asian countries were 35 times more likely to develop TB than general population ( 50 ).…”

“…TB infection following ICIs therapy lacks specificity, and is usually characterized by cough, expectoration, breathlessness, fever and weight loss ( 49 , 53 ). Imaging manifestations, from chest X-ray and contrast CT, support the diagnosis with features like new consolidation, patchy opacity/nodules, or the tree-in-bud sign, especially in the upper lobes ( 49 ). However, confirmation is achieved by culture of MTB or DNA detection by polymerase chain reaction (PCR) ( 52 , 55 ).…”

“…Excessive inflammatory cells and cytokines destroy the extracellular matrix, favoring the growth of MTB, which breaks the state of latent infection and leads to the reactivation of TB (53). TB infection following ICIs therapy lacks specificity, and is usually characterized by cough, expectoration, breathlessness, fever and weight loss (49,53). Imaging manifestations, from chest X-ray and contrast CT, support the diagnosis with features like new consolidation, patchy opacity/nodules, or the tree-in-bud sign, especially in the upper lobes (49).…”