Mir-34a as predictor of immunotherapy efficacy in NSCLC patients.

e21191 Background: MicroRNAs are critical modulators of the immune response and regulate the expression of various immune checkpoints during immunotherapy. In the present study we evaluated the predictive significance of immune related miRNAs in the plasma of non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors. Methods: Plasma was obtained from 62 NSCLC patients before the initiation of immunotherapy, administered as second- or third-line treatment. The expression profile of immune-related miR-34a, miR-146a, miR-155, miR-200b, miR-202 and miR-223 was assessed by RT-qPCR. Patients were classified in high and low expression groups according to the median value of each miRNA. Patients that had achieved partial response (PR) or stable disease (SD) were classified as responders, whereas patients with progressive disease (PD) were classified as non-responders. Results: No statistical correlations were observed among miRNA expression and clinical outcomes in the whole group of patients (N = 62). However, in the non-squamous subgroup (N = 36) lower miR-34a expression levels were observed in non-responders compared to responders (80% vs 20%; p = 0.029). Univariate binary logistic regression analysis revealed that only low miR-34a expression (HR: 8.000, 95% CI: 1.215-52.693; p = 0.031) was correlated with the probability of developing progressive disease as best response to immunotherapy. Patients with low miR-34a expression levels were associated with shorter progression free survival (PFS) and overall survival (OS) compared to patients with high 34a expression (1.97 vs 6.33 months; p = 0.042 and 2.93 vs 9,60 months; p = 0.012, respectively). Furthermore, low miR-34a expression emerged as an independent predictor of shorter PFS and OS (HR: 2.449; p = 0.049 and HR: 3.203; p = 0.016, respectively). No other correlations were observed among the rest of the miRNAs and clinical outcomes. Conclusions: Our findings suggest that circulating miR-34a may serve as a potential predictive biomarker in NSCLC patients treated with immunotherapy. These observations need to be further validated in a larger cohort of patients.