Factors Associated with Active Tuberculosis Disease in Patients with Lung Cancer Following Immune Checkpoint Blockade Therapy: A Retrospective Cohort Study and Case Reports

Xiao Wang,1 Yu-Xiao Wu,1,2 Wei-Ping Hu,1 Yue Ren,1 Jing Zhang11Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Peking University First Hospital, Beijing, People’s Republic of ChinaCorrespondence: Jing Zhang, Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China, Email zhang.jing@zs-hospital.sh.cnBackground: Immune checkpoint inhibitors (ICIs) have revolutionized lung cancer treatment by improving survival in patients with advanced disease and expanding treatment options for patients with early-stage disease. However, ICIs may increase the risk of active tuberculosis (TB) disease. Our study investigated potential warning markers for active TB disease in patients with lung cancer receiving ICIs, aiming to inform management strategies.Methods: A retrospective cohort study at Zhongshan Hospital of Fudan University reviewed 4157 solid tumor patients treated with ICIs from January 2021 to February 2023. A total of 118 patients with lung cancer were included, either diagnosed with latent TB infection or non-active TB, or had a confirmed TB history before the start of ICI therapy. The primary outcome was the occurrence of active TB disease, with follow-up extending to February 1, 2024. Propensity score matching (PSM) was applied to account for differences in baseline characteristics.Results: Among the 118 patients, 5 (4.24%) developed active TB. Post-PSM Fisher’s exact test suggested that confirmed TB history (RR: 4.00, p = 0.029), high tumor necrosis factor-alpha (RR: 8.64, p = 0.030), high interleukin-2 receptor (RR: 6.00, p = 0.031), low white blood cell count (RR: 8.50, p = 0.009), and low lymphocyte count (RR: 9.33, p = 0.014) were significantly associated with active TB disease. Among patients who developed active TB disease, two had a decrease in T-SPOT.TB spot count after receiving ICI therapy.Conclusion: The identification of significant factors associated with active TB underscores the importance of vigilant monitoring and early intervention. A decrease in the T-SPOT.TB spot count may not necessarily reflect an improvement in TB infection, but may instead indicate potential TB activation.Keywords: immunotherapy, immune checkpoint inhibitors, lung cancer, infection, tuberculosis