Circulating cytokines associated with clinical outcomes in advanced non-small cell lung cancer patients who received chemoimmunotherapy

Background: Pretreatment and on-treatment plasma cytokine levels in predicting clinical benefit in patients with advanced non-small cell lung cancer (NSCLC) treated with anti-programmed death-1 (PD-1)-based chemotherapy is still a matter of debate.

Methods: We measured 12 kind of plasma cytokines in patients with stage III/IV NSCLC before and during treatment with anti-PD-1 based chemotherapy. Associations with best overall response, and survival including progression-free survival (PFS) and overall survival (OS) were assessed using Chi-square test and Kaplan-Meier plots with log-rank test, respectively. Logistic regression and Cox regression were used to determine independent risk factors.

Results: Of a total of 60 patients, high-level of pretreatment interleukin-2 was associated with longer PFS (log rank p = 0.049), while high-level of pretreatment interleukin-8 was associated with shorter OS (log rank p = 0.006). Increased on-treatment interleukin-1β (IL-1β) was associated with both better response (odds ratio [OR] 6.233, 95% confidential interval [CI]: 1.451-26.344, p = 0.013) and longer PFS (hazard ratio [HR] 0.305, 95% CI: 0.127-0.730, p = 0.008). On the contrary, increased on-treatment interleukin-6 (IL-6) was associated with a worse response (OR 0.015, 95% CI: 0.001-0.400, p = 0.012), worse PFS (HR 2.639, 95% CI: 1.163-5.991, p = 0.020) and worse OS (HR 2.742, 95% CI: 1.063-7.074, p = 0.037). Increased interferon-γ (IFN-γ) was found to be associated with better PFS (HR 0.336, 95% CI: 0.153-0.745, p = 0.007).

Conclusions: In patients with advanced NSCLC who received chemoimmunotherapy, on-treatment increased IL-1β and IFN-γ may serve as positive indicator of efficacy, while on-treatment increased IL-6 might play a predictive role of worse clinical outcome.