Paradoxical response in a patient with non-small cell lung cancer who received nivolumab followed by anti-Mycobacterium tuberculosis agents

Abstract

Anti-programmed cell death-1 (PD-1) agents enhance the antitumor immunoresponse. A number of reports have indicated that patients with malignancies who receive anti-PD-1 agents are at risk for tuberculosis (TB) infection. In this report, we present a patient with non-small cell lung cancer who developed pulmonary tuberculosis while receiving the anti-PD-1 agent nivolumab, and who subsequently demonstrated a paradoxical response (PR) 10 days after initiation of anti-MTB treatment. We suggest that anti-PD-1 agents not only induce the development of pulmonary TB, but also development of PR after anti-MTB treatment, through upregulation of the immune response. Furthermore, based on their radiological and immunological similarity, we speculate that the schema of development of PR closely resembles that of pseudoprogression in non-small cell lung cancer patients after anti-PD-1 treatment.

Pulmonary complications of immune checkpoint inhibitors in patients with nonsmall cell lung cancer

“…Patients who developed pulmonary TB while receiving an ICI were mostly males treated with anti-PD-1 inhibitors for NSCLC. TB occurred relatively early after ICI initiation, with a 15 (4-33)-week median delay of onset, in the absence of any other immunosuppression agent except cancer [135][136][137][138][139][140][141]. This suggests reactivation of prior latent TB rather than rapid progression to TB of a recent de novo infection.…”

“…Among the nine pulmonary TB cases reported under ICI treatment [135][136][137][138][139][140][141], nearly half were asymptomatic, and the TB was revealed during a thoracic CT scan performed for the cancer follow-up. Clinical symptoms and radiological findings may have been confused with cancer progression.…”

“…However, thoracic CT scan imaging was as usual revealing nodules, cavitary lesions and pleural effusion [143], and positivity of direct examination or culture of sputum for Mycobacterium tuberculosis was rather common when performed. Pulmonary TB occurrence often led to ICI discontinuation (eight cases out of nine), along with anti-TB treatment [135][136][137][138][139][140][141]. However, two of the nine reported cases died [135,140].…”

Development of tuberculosis in cancer patients receiving immune checkpoint inhibitors

“…Interestingly, the occurrence of tuberculosis (TB) after ICI use has been steadily increasing [6][7][8][9][10][11][12][13]; however, no previous reports have studied the development of TB associated with the use of ICIs in a large cohort. Therefore, we investigated the occurrence of TB after starting ICIs among a large cancer-patient cohort.…”

Multifocal Tuberculosis with Prolonged Paradoxical Reaction

“…Takata et al, 2019 [20] Lung A patient with small cell lung cancer, three days after completing a course of chemotherapy, he developed fever, cough with purulent sputum and diagnosed with pulmonary TB. Ten days after starting anti-TB therapy he developed fever, tachycardia and the size of the original opacities increased, and new lung opacities developed.…”