Serum sCD25 Protein as a Predictor of Lack of Long-Term Benefits from Immunotherapy in Non-Small Cell Lung Cancer: A Pilot Study

SIMPLE SUMMARY: The prognosis of advanced lung cancer is poor. Even though it can improve with immunotherapy, most patients do not respond to treatment. Identifying patients who would not benefit from therapy is an unmet goal. We hypothesized that one of the molecules present in human serum (namely, the soluble form of the unit α of the interleukin-2 receptor, sCD25) could be used as a predictor of successful immunotherapy in patients with lung cancer. Our study showed that patients who presented high sCD25 levels before treatment (≥5.99 ng/mL) and/or about three months from the start of treatment (≥7.73 ng/mL) progressed faster and lived shorter without the disease progression and serious toxicity. Serum levels of sCD25 could easily indicate patients with lung cancer who would not achieve long-term benefits from immunotherapy. Therefore, other more effective therapies could be implemented. ABSTRACT: Prognosis of advanced non-small cell lung carcinoma (NSCLC) is poor. Even though it can improve with anti-PD-1/PD-L1 agents, most patients do not respond to treatment. We hypothesized that the serum soluble form of the unit α of the interleukin-2 receptor (sCD25) could be used as a biomarker of successful immunotherapy in NSCLC. We recruited patients dosed with atezolizumab (n = 42) or pembrolizumab (n = 20) and collected samples at baseline and during the treatment. Levels of sCD25 were quantified with the ELISA kits. Patients with a high sCD25 at baseline (sCD25.0 ≥ 5.99 ng/mL) or/and at the end of the fourth treatment cycle (sCD25.4 ≥ 7.73 ng/mL) progressed faster and lived shorter without the disease progression and serious toxicity. None of the patients with high sCD25 at both time points continued therapy longer than 9.3 months, while almost 40% of patients with low sCD25 were treated for ≥12.3 months. There was a 6.3-times higher incidence of treatment failure (HR = 6.33, 95% CI: 2.10–19.06, p = 0.001) and a 6.5-times higher incidence of progression (HR = 6.50, 95% CI: 2.04–20.73, p = 0.002) in patients with high compared with low sCD25.0 and sCD25.4. Serum levels of sCD25 may serve as a non-invasive biomarker of long-term benefits from the anti-PD-1/PD-L1s in NSCLC.