The association between BIM deletion polymorphism and treatment efficacy of PD-1/PD-L1 inhibitors in advanced NSCLC.

Abstract

e21055 Background: PD-L1 is a recommended biomarker for immunotherapy, but Some patients with high pD-L1 expression had poor clinical response. Considering the inconsistent correlation between PD- L1 expression and ICI efficacy, A more sensitive biomarker is needed to predict immunotherapy efficacy. B-cell lymphoma-2 (BCL2L11/BIM) belongs to the Bcl-2 family and is a key factor promoting apoptosis. BIM deletion polymorphism (BIM- del) may lead to BH3 deletion and thus hinder cell apoptosis. Loss and decreased expression of BIM may lead to resistance to tumor therapy. A study on patients with metastatic melanoma found that the high level of BIM in CD8+ T cells suggests a stronger PD-1 and PD-L1 interaction, which predicts clinical benefit in patients with metastatic melanoma receiving anti-PD-1 therapy.This study aims to evaluate the relationship between BIM deletion and PD-1/PD-L1 inhibitors efficacy in advanced NSCLC patients. Methods: Patients diagnosed with advanced stage NSCLC that treated with Immune checkpoint inhibitors (ICIs) at Shandong Cancer Hospital between March 2019 and January 2021 were enrolled in this study. Peripheral blood samples from these patients were collected to detect BIM-del by polymerase chain reaction. Cox proportional hazards models were used to analyze the clinical outcomes of patients with and without BIM-del. Results: A total of 61 patients with advanced NSCLC who received immunotherapy were enrolled, only 18.0% (11/61) patients were detected with BIM-del. Most of the patients were male (73.8%, 45/61), younger than 65 years (72.1%, 44/61), non- smokers (50.8%, 31/61), previous treatment lines 0-1 (90.2%, 55/61),had Eastern Tumor Cooperative group (ECOG) performance status (PS) 0-1 (98.4%, 60/61). There were no associations between the BIM-del and clinical characteristics. There was no difference in the objective response rate between patients with and without BIM-del (27.3% vs 30 %, p = 1.000).BIM-del is associated with shorter progression-free survival (PFS) (5.7 months vs12.0 months, p = 0.001). The median OS had not been reached. Multivariate analysis suggested that BIM-del was an negative independent prognostic factor for PFS in immunotherapy patients with non-small cell lung cancer, but not for OS. Conclusions: BIM-del may be a negative prognostic biomarker for patients with advanced NSCLC treated with immunosuppressive therapy. It is very important to find effective and accurate biomarkers to predict the PD-1/PD-L1 inhibitors Treatment efficacy, and further exploration is needed in the future.