Post-treatment serum IL-6 independently associated with progression in observational cohort of advanced NSCLC with COPD

Higher serum interleukin-6 (IL-6) measured after six cycles of systemic therapy was independently associated with tumor progression in a two-center observational cohort of 120 patients with advanced non-small cell lung cancer (NSCLC) and coexisting COPD. The multicenter cohort was conducted from 1 May through 31 December 2025 at the Najaf National Cancer Center and the Al-Diwaniyah Oncology Center in Iraq. Eligible patients had histologically confirmed NSCLC and coexisting COPD, had completed six cycles of systemic therapy, and had clinical, radiological and laboratory data available.

Patients were excluded if they had incomplete data, acute infection or inflammatory conditions, autoimmune disease or another concurrent malignancy. They received chemotherapy alone (n=31), pembrolizumab plus chemotherapy (n=39), or atezolizumab plus chemotherapy (n=50), with treating oncologists making treatment decisions according to institutional clinical practice guidelines. The three groups did not differ significantly in baseline age, sex, smoking status or PD-L1 expression.

Tumor response was evaluated using RECIST version 1.1, while pulmonary function was assessed by forced expiratory volume in 1 second as a percentage of predicted value. Blood was collected on day 10 after the sixth treatment cycle between 9:00 and 10:00 a.m. Serum IL-6 was measured with an enzyme-linked immunosorbent assay, for which the reported detection range was 4.69–300 pg/mL and sensitivity was 2.8 pg/mL.

Patients were also assessed with routine blood counts, including hemoglobin, platelet count and neutrophil-to-lymphocyte ratio (NLR). Response distributions differed significantly among the treatment groups (p < 0.001). Progressive disease occurred in 48.4% of the chemotherapy group, 15.4% of the pembrolizumab group and 8.0% of the atezolizumab group.

Objective response, comprising complete or partial response, was reported in 16.1%, 61.5% and 60.0% of the respective groups. Disease control, defined as complete response, partial response or stable disease, was 51.6%, 84.6% and 92.0%, respectively. These were descriptive comparisons in nonrandomized treatment groups and do not establish comparative treatment efficacy.

Median post-treatment IL-6 concentrations also differed by treatment group: 16.5 pg/mL with chemotherapy, 12.5 pg/mL with pembrolizumab plus chemotherapy and 10.0 pg/mL with atezolizumab plus chemotherapy (p < 0.001). When patients were grouped by response, those with complete or partial response had a median IL-6 concentration of 9.23 pg/mL, compared with 15.7 pg/mL among those with stable or progressive disease (p < 0.001). These values were group medians with interquartile ranges, rather than average concentrations.

Receiver operating characteristic analysis estimated the ability of post-treatment IL-6 to discriminate progressive disease from non-progressive disease, with an area under the curve of 0.961 (95% confidence interval, 0.909–0.988). A threshold above 15.5 pg/mL had a reported sensitivity of 91.6% and specificity of 96.0%. This was an in-sample analysis in the treated cohort, and the reported performance has not established IL-6 as a validated clinical test.

Multivariable logistic regression retained an association between IL-6 and progressive disease. For each 1 pg/mL increase in IL-6, the adjusted odds ratio for progression was 1.72 (95% confidence interval, 1.34–2.21; p < 0.001). The NLR was associated with progression in the univariate analysis, with an odds ratio of 3.00 per one-unit increase (95% confidence interval, 1.88–4.80; p < 0.001), but it was not independently associated after adjustment (adjusted odds ratio 1.39; 95% confidence interval, 0.79–2.44; p=0.24).

Platelet count and FEV1 as a percentage of predicted also were not independently associated with progression. The findings are observational and do not establish that elevated IL-6 causes progression, that IL-6 is a cause-specific marker, or that measuring it would improve clinical decisions. The study did not assess longitudinal changes in IL-6, and the sample of 120 patients may limit subgroup analyses and generalizability.

All participants had COPD, and the results came from two Iraqi oncology centers, so applicability to patients without COPD or to other health systems requires assessment. The authors stated that the findings require confirmation in larger prospective longitudinal studies before IL-6 can be incorporated routinely into risk stratification or used to guide treatment decisions.

Subject of Research: Post-treatment serum IL-6 and progression in advanced NSCLC with COPD

Article Title: Post-treatment serum interleukin-6 is independently associated with disease progression in patients with advanced non-small cell lung cancer and coexisting COPD: a multicenter real-world cohort study

Article References: Kareem, A. H., Mohammed, S. I., & Shihad, A. A. (2026). Post-treatment serum interleukin-6 is independently associated with disease progression in patients with advanced non-small cell lung cancer and coexisting COPD: a multicenter real-world cohort study. Pharmacia, 73, Article e194159. https://doi.org/10.3897/pharmacia.73.e194159

Image Credits: AI Generated

DOI: 10.3897/pharmacia.73.e194159

Keywords: NSCLC, COPD, interleukin-6, disease progression, chemotherapy, immune checkpoint inhibitors, observational cohort, risk stratification, Post-treatment, serum, independently, associated