Respiratory toxicities after concurrent chemoradiotherapy and subsequent consolidation immune checkpoint inhibitors in locally advanced non-small cell lung cancer: Infectious and non-infectious subtypes by pathogen NGS testing.

Abstract

e20557 Background: Consolidation immune checkpoint inhibitors (ICIs) following concurrent chemoradiotherapy (CCRT) have significantly improved survival in locally advanced non-small cell lung cancer (LA-NSCLC), while the associated respiratory toxicities were of particular concern. We aimed to investigate the > = G2 respiratory toxicities, the characteristics of concomitant infection, and provide detailed information for clinical management. Methods: We reviewed 77 LA-NSCLC patients treated with CCRT and consolidation ICIs. The details of > = G2 respiratory toxicities and concomitant infection were analyzed. Potential risk factors for > = G2 respiratory toxicities were explored by univariable and multivariable analysis. Respiratory toxicities were collected from the start of consolidation ICIs till 6 months after the last infusion of ICIs. Concomitant infection was defined as positive findings from next-generation sequencing (NGS) of bronchoalveolar lavage sampling. Results: Patients were treated with definitive radiotherapy at a median dose of 60 Gy (IQR, 60-64), concurrently with weekly docetaxel and platinum and followed by single-agent ICIs. The median duration of consolidation ICIs was 5.4 months (IQR, 2.3-8.2). Twenty-six patients (33.8%) experienced > = G2 respiratory toxicities by a median of 4.8 months (IQR 1.5-6.6) after initiation of consolidation ICIs. Pneumonitis (14, 18.2%) and tracheobronchitis (13, 16.9%) were the most common > = G2 respiratory disorders. Location of primary tumor (p = 0.027) and the proportion of CD3+ lymphocyte before consolidation ICIs (p = 0.044) were independent risk factors for the occurrence of > = G2 respiratory toxicities. Eleven patients (14.3%) had > = G2 respiratory toxicities and concomitant infection. Identified pathogens included bacteria (n = 9), Aspergillus (n = 5), Pneumocystis (n = 1) and Leptosvirus (n = 1). Concomitant infection was more commonly detected in patients with tracheobronchitis compared with those with pneumonitis ( p= 0.002), was associated with a higher grade of toxicity ( p= 0.050) and relatively poorer outcome after management ( p= 0.002). Conclusions: Respiratory toxicities after CCRT and subsequent consolidation ICIs in LA-NSCLC mainly included pneumonitis and tracheobronchitis, and could be separated into infectious and non-infectious subtypes. Bacteria and Aspergillus were the predominant pathogens. Our findings highlight the importance of the bronchoscopy and pathogen NGS testing to detect airway disease and specific infection. Long-term systemic steroids might adversely affect respiratory toxicities with concomitant opportunistic infection, which should be taken into account at the onset of management.