Treatment response and safety of immunotherapy for advanced non-small cell lung cancer with comorbid chronic obstructive pulmonary disease: a retrospective cohort study

Background: Immunotherapy has provided a novel therapeutic option for lung cancer but studies involving patients with advanced non-small cell lung cancer (NSCLC) coupled with various degrees of comorbid chronic obstructive pulmonary disease ( COPD) are limited. Thus, we performed a retrospective cohort study to optimize the use of immunotherapy in this special population. Methods: We enrolled a total of 99 patients with advanced ( stage IIIB/C-IV) NSCLC with comorbid COPD who had received immune checkpoint inhibitors (ICIs) according to the inclusion and exclusion criteria. They were divided into four groups according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guideline criteria as follows: no COPD group (n1=19), mild COPD group (n2=24), moderate COPD group (n3=31), and severe COPD group (n4=25). Routine blood, imaging characteristics, related cytokines including interleukin (IL)-6, IL-8, IL-10, etc., Krebs Von den Lungen (KL)-6, and corresponding indicators of immune-related adverse events (irAEs), incidence of irAEs, objective response rate (ORR), disease control rate (DCR) and progression-free survival (PFS) were recorded and analyzed. Comparability of baseline factors above and clinical characteristics were evaluated. Results: There were statistically significant differences in the incidence of irAEs among the four groups (P=0.003). The incidence of irAEs in patients with no COPD (n(1), 21.1%) and mild to moderate COPD (n(2/3), 8.3%, 32.3%) was lower than that in patients with severe COPD (n(4), 56.0%) (P=0.003). The median PFS of the mild to moderate COPD group was significantly longer than the severe COPD group (19.0 vs. 8.00 months, log-rank P=0.004). A significant increase of both ORR (P=0.004) and DCR ( P= 0.037), as well as higher IL-6 (P=0.000), IL-8 (P=0.026), and IL-10 ( P=0.010) levels, have been observed in the mild to moderate COPD group compared with severe COPD group. IL-6 level was an independent factor influencing PFS [ P= 0.007, 95% confidence interval (95% CI): 1.000-1.002] and COPD grading was an independent predictor of irAEs (P=0.037, 95% CI: 1.035-3.039). Conclusions: Immunotherapy should be selected with caution for advanced NSCLC patients with comorbid severe COPD, considering the limited efficacy and the increased risk of immune-related adverse events related to the immune-checkpoint inhibitors administration in this special population.