Lack of Reactivation of Latent Tuberculosis despite PD-1 Immunotherapy and Chemotherapy: A Case Report and Systematic Review

Case Report

Austin J Gastroenterol. 2024; 11(1): 1128.

Lack of Reactivation of Latent Tuberculosis despite PD-1 Immunotherapy and Chemotherapy: A Case Report and Systematic Review

Xiaojuan Yang¹; XingHong Xian²; Qing Zhu¹; Ke Wang2,3*

1Abdominal Oncology Ward, Cancer Center, West China Hospital, Sichuan University, Chengdu, China

2Department of Pulmonary and Critical care Medicine, West China Hospital, Sichuan University, Chengdu, China

3Lung Cancer Center, West China Hospital, Sichuan University, Chengdu, China

*Corresponding author: Ke Wang Division of Respiratory Medicine, Lung Cancer Center, West China Hospital, Sichuan University, No. 37 Guo Xue Xiang, 610041 Chengdu, China. Tel: +18980602252; Fax: 00862155666857 Email: wang2ke@126.com

Received: December 01, 2023 Accepted: January 04, 2024 Published: January 11, 2024

Abstract

Background: Programmed Death 1 (PD-1) has a controversial role in the treatment of Tuberculosis (TB). Several clinical cases of TB development have been reported by administration of anti–PD-1 antibodies for patients with advanced unresectable cancers.

Case presentation: In this article, we report an interesting case about a male patient with history of cured pulmonary tuberculosis and a 4-month history of repeated hemoptysis. Imaging showed one mass in the lower lobe of left lung and the other in the left upper lobe. The diagnosis of Non-Small-Ccell Lung Cancer (NSCLC) was determined by biopsy specimens in the lower lobe nodule and cured pulmonary tuberculosis determined by past medical history. He was given neoadjuvant treatment with an anti–PD-1 inhibitor and chemotherapy. He underwent surgery. Pathological examination revealed Mtb in left upper lobe nodule but previous imaging showed without reactivation and slight reduction in tubercular infection inflammation. The left lower lobe nodule was poorly differentiated carcinoma.

Conclusions: Overall, the role of immune checkpoint inhibitors in patients with cancers and latent tuberculosis infection is inconclusive. Although we cannot establish whether patients with stage IIIA NSCLC and concurrent latent pulmonary tuberculosis after surgical evaluation can receive a PD-1 and chemotherapy as neoadjuvant therapy without the activation of pulmonary tuberculosis, our case endorses the need of further evaluation.

Keywords: NSCLC; PD-1 inhibitors; reactivation; Mtb

Abbreviations: PD-1: Programmed Death 1; Mtb: Mycobacterium Tuberculosis; NSCLC: Non-Small-Cell Lung Cancer; irAEs: Immune-related Adverse Events; pPR: Part Pathological Rresponse; 18F-FDG PET-CT: 18F-Fluorodeoxyglucose Positron Emission Tomography Combined with Computed Tomography

Background

Approximately 35% of Non-Small Cell Lung Cancer (NSCLC) patients are considered locally advanced non-metastatic disease at the time of diagnosis [1]. After surgical evaluation, patients may be treated with induction chemotherapy as a standard-of-care treatment for cT4N0M0, clinical stage IIIA. A recent report evidenced that neoadjuvant administration of two doses of Programmed Death 1 (PD-1) inhibitors in surgically resectable NSCLC (stage I, II, or IIIA) led to a major pathological response in about half of tumor (45%) without delays in planned surgery [2].

On the other hand, checkpoint inhibitors including PD-1 inhibitors can induce immune-related adverse events (irAEs) which can affect normal tissues [3]. Multiple cases of tuberculosis after immunotherapy have been observed [4-8], but all types of cancer are unresectable, including relapsed and metastatic diseases. Here, we report a stage IIIA NSCLC patient with concurrent pulmonary tuberculosis having a Pathological Part Response (pPR), but without the activation of pulmonary tuberculosis after the neoadjuvant treatment with pembrolizumab and chemotherapy.

Case Presentation

A 60-year old male patient with history of cured pulmonary TB was admitted to West China Hospital of Sichuan University in October 2019. He was a never smoker and with a 4-month history of repeated hemoptysis, but without other relevant clinical details such as fever, chest pain, anorexia, and weight loss. For previous pulmonary TB, he suffered from this disease in 2016 and was cured with a three-drug regimen for one year at an outside institution. The 18F-fluorodeoxyglucose (18F-FDG) Positron Emission Tomography (PET) combined with computed tomography PET-(CT) images showed intense uptake at the mass in the dorsal segment of lower lobe of left lung whose maximum cross section was approximately 6.4×5.3cm (Figure 1A and B] and which invades the apical and posterior segment of the left upper lobe and adjacent pleural (SUVmax 16.21) (Figure 1C). In the remaining lobes of bilateral lungs, there are many solid nodules, streak shadows, patch shadows, consolidation shadows and light transmission areas without lung texture. The nodules are mainly located in the bilateral upper to middle lobes, and most of them are distributed in clusters, with calcification. The largest nodule is located in another part of the apical and posterior segment of the left upper lobe which was measured 1.3×0.8cm, with faint uptake (SUVmax 2.13) (Figure 2A and 2B). 18F-FDG PET/CT scanning demonstrated without lymph node involvement. Unfortunately, the initial investigations for pulmonary TB such as sputum examination for acid-fast bacilli and GeneXpert were not performed. CT-guided, trans-cutaneous fine-needle aspiration was taken on the dorsal segment of lower lobe of left lung nodule. Immunohistochemistry staining revealed that he had a poorly differentiated lung adenocarcinoma, with pan-cytokeratin (PCK) (+) (Figure 3A), cytokeratin (CK) 7 (+) (Figure 3B), Epithelial Membrane Antigen (EMA) (+) (Figure 3C), thyroid transcription factor-1 (TTF-1) (+) (Figure 3D), cytokeratin (CK) 5/6 (-), Desmin (-), S-100 (-), Synaptophysin (Syn) (-), P63 (-), Chromogranin A (CgA) (-), ALK-V (-), ROS-1 (-). After systemic evaluation, he was diagnosed with poorly differentiated adenocarcinoma, cT4N0M0, clinical stage IIIA lung cancer based on the AJCC Cancer Staging Manual, Eighth Edition (2018). Thoracic surgeon suggested neoadjuvant treatment instead of upfront surgery. The patient received two cycles of neoadjuvant treatment with a PD-1 inhibitor pembrolizumab 200 mg (2 mg/Kg) plus carboplatin area under curve 5 mg/mL per min and pemetrexed 500 mg/m2 in cycles of once every 3 weeks (Figure 2E). Subsequently, the PET-CT scans revealed marked reduction of FDG uptake in the previous involved fine-needle aspiration nodule (SUVmax 2.35 compared with 16.21 at the outset) (Figure 1D, E and F) and slight reduction in another nodule (SUVmax 1.66 compared with 2.13 at the outset) (Figure 2C and D). Then he underwent left lower lobectomy and left upper wedge resection with mediastinal lymph node dissection for lung cancer. Pathological examination revealed Mycobacterium TB (Mtb) in left upper lobe nodule and TB A polymerase chain reaction (TB-qPCR) detection Mtb DNA fragments. In addition, positive acid-fast stain was observed in that surgical specimens (Figure 4A). The pathologic specimens in the left lower lobectomy revealed that poorly differentiated carcinoma with massive necrosis areas where there was only remaining 10% tumor tissues (Figure 4B). Circulating tumor cells prior to operation also did not be found (CTCs) in this patient.