Autologous natural killer cell infusion as consolidation therapy after first-line chemoradiotherapy for limited-stage small-cell lung cancer: A randomized, controlled, open-label, single-center phase II clinical study.

8013 Background: Small-cell lung cancer (SCLC) grows rapidly, is aggressive, has a poor prognosis, and tends to recur after treatment. Autologous cellular immunotherapy (CIT) has demonstrated good safety and efficacy across various tumors; however, there are no prospective studies utilizing autologous natural killer (NK) cells for consolidation therapy following first-line chemoradiotherapy for SCLC. Methods: This study aimed to evaluate the safety and efficacy of autologous NK cell infusion (administered every 2 weeks for a total of six courses) as consolidation therapy after first-line standard treatment for limited-stage SCLC, compared to routine follow-up in a randomized, controlled, open-label, single-center phase II clinical trial. The primary endpoint was progression-free survival (PFS, assessed according to Response Evaluation Criteria in Solid Tumors version 1.1), while secondary endpoints included overall survival (OS), the 12- and 24-month PFS rate, the 24- and 36-month OS rate and safety. Results: Forty-three patients with limited-stage SCLC were included in the final analysis, comprising 21 patients in the treatment group who received autologous NK cell infusion after chemoradiotherapy and 22 patients in the control group who underwent routine follow-up. At 6 months, the response to initial chemoradiotherapy was maintained in 27.3% (6/22) of the control patients and 57.1% (12/21) of the treatment patients. The objective response rate (ORR) and PFS rates at 12 months for controls compared to treatment patients were 0% versus 19.0% (4/21) (P < 0.05) and 4.5% (1/22) versus 42.9% (9/21) (P < 0.01), respectively. Compared to the control group, the autologous NK cell consolidation group achieved significantly longer PFS (median 6.5 vs. 11.92 months; hazard ratio HR 0.38, 95% confidence intervals CI 0.18 to 0.79; P = 0.01) and OS (median 15.6 vs. 27.13 months; HR 0.41, 95% CI: 0.19 to 0.87, P = 0.02), with a particularly pronounced PFS benefit when calculated from the end of chemoradiotherapy (median 8.1 vs.16.3 months; HR 0.35, 95% CI 0.17 to 0.72, P = 0.01). Regarding safety, the incidence of all adverse events (AEs) due to any cause was 50.0% (11/22) in the observation group and 47.6% (10/21) in the treatment group, with most being grade 1–2 and considered unrelated to NK cell infusion. NK cell treatment exhibited good overall safety and tolerability. Additionally, we characterized changes in peripheral blood cell subsets and metabolites before and after treatment, as well as the tumor immune microenvironment characteristics in patients from the treatment group. Conclusions: Autologous NK cell infusion as consolidation therapy after first-line chemoradiotherapy for SCLC yielded promising preliminary PFS and OS results, with a well-tolerated safety profile. Clinical trial information: NCT03410368 .