A Tragic Trifecta: A Cautionary Tale of Fatal Pulmonary Tuberculosis in a Patient on PD-L1 Inhibitor Therapy for Non Small Cell Lung Cancer

Abstract INTRODUCTION: Since the discovery of the Programmed cell death protein (PD-1) on T cells in 1992, and its binding site on human cells, the Programmed Cell DeathLigand- 1 (PD-L1), this unique pathway of apoptosis has been extensively studied for its therapeutic applications, especially immunotherapy for solid tumors. The KEYNOTE clinical trial led to the FDA approval of thePD-1 inhibitor Pembrolizumab for NSCLC marking a significant breakthrough in lung cancer treatment.However, the use of these immune checkpoint inhibitors has been associated with an increased risk of tuberculosis and atypical mycobacterial infections. This side effect is thought to result fromPD-1/PD-L1 inhibition, which enhances Th1 activity and leads to T cell exhaustion, impairing immune surveillance. As such, prevention and early detection of mycobacterial infection among patients on immune checkpoint inhibitors is paramount.Here we present a case of fatal pulmonary tuberculosis in a patient soon after initiation of PD-L1 inhibitor Durvalumab and highlight the importance of appropriate testing. CASE: Then aged 60, this gentleman with a 50 pack year smoking history was diagnosed with Squamous Cell Lung Cancer 3 years ago and initiated on chemotherapy. The next 3 years were marked with frequent hospitalizations at different facilities for pneumonia treated with antibiotics. TB testing via BALs was supposedly negative during one such hospitalization. He was subsequently initiated on adjunctive immunotherapy with Durvalumab for metastatic lung cancer, with plans for maintenance therapy out-patient. Another episode of severe pneumonia led to a diagnosis of PulmonaryHistoplasmosis via a positive urine antigen test; he was started on itraconazole and discharged with home oxygen for his progressive COPD. Despite compliance with therapy, his condition continued to worsen prompting an ER visit for 1 week of fever, cough productive of copious sputum and increasing oxygen requirements. Initial hypotension rapidly responded to IV fluid resuscitation and empiric antibiotics were initiated.Imaging revealed a RUL consolidation with cavitation and multiple patchy opacities in both lungs. Considering his immunocompromised state, TB testing was sought and sputum cultures were positive for 4+ AFB, confirming a diagnosis of Pulmonary tuberculosis.RIPE therapy was initiated with rapid improvement in symptoms over the next week. He was discharged with appropriate follow-up and transfer of information to his oncologist. However, he was re-admitted soon after and passed away with comfort measures per family's wishes.