Relationship between immune-inflammatory markers and clinical features and deepness of tumor response and prognosis of patients with PD-L1 ≥50% metastatic NSCLC receiving first-line immunotherapy.

Abstract

e14547 Background: Patients with programmed cell death-ligand 1 (PD-L1) ≥50% metastatic non-small cell lung cancer (NSCLC) treated with first-line immunotherapy have heterogeneous clinical assessment and outcomes. In this study, we sought to identify features of patients with metastatic NSCLC who achieved high deepness of response (HDPR) to first-line immunotherapy, and how these might differ from features predictive of non-high deepness of response (NHDPR). The influence of clinical features on prognosis of patients with PD-L1 ≥50% were further clarified. Methods: This retrospective study analyzed patients with PD-L1≥50% metastatic NSCLC treated with first-line immunotherapy at Beijing Tiantan Hospital between July 2020 and December 2023. All the patients had at least one measurable lesion in lung according to the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. HDPR was defined as deepness of lung tumor response ≥50%, while NHDPR was defined as deepness of lung tumor response <50% or tumor enlargement. Tumor PD-L1 expression, target mutation, neutrophil-to-lymphocyte ratio (NLR), lactic dehydrogenase (LDH) level, and other prognostic variables were analyzed to identify characteristics enriched in patients achieving HDPR compared to NHDPR. We also investigated the effects of these variables on first-line progression-free survival (PFS) and overall survival (OS) of the patients. Results: A total of 17 patients were included in our retrospective analysis. Seven (41.2%) patients achieved HDPR (range: -50%, -72%) and ten (58.8%) patients achieved NHDPR (range: -13%, -45%). Seven (41.2%) patients had central nervous system (CNS) metastases at the first diagnosis of lung malignancy, and their CNS target lesions shrinkages were observed after therapy (range: -32%, -100%). Lower Th/Ts ratio ( P=0.01) and drug resistance mutations (TP53/KRAS/EGFR) ( P=0.001) were found enriched for NHDPR compared to HDPR. However, no differences were found in tumor PD-L1 expression, NLR, LDH, B lymphocyte subset, NK cell subset, pathological type, T-stage, smoking index, ECOG score, immunotherapeutic schemes, or CNS metastases between the two groups ( P>0.05). With a median follow-up of 26.0 months (range: 17.2-34.8 months), the median first-line PFS and OS were 9.0 months (95% CI: 5.0-13.0) and not reached (NR), respectively. The NLR was identified as an independent prognostic factor on first-line PFS. Patients with an NLR≥4 exhibited a worse median PFS (7.0 months vs. NR; P=0.033; 95%CI: 1.2-80.2) than those with an NLR<4 following first-line immunotherapy. Conclusions: Among patients with PD-L1≥50% metastatic NSCLC who received first-line immunotherapy, lower Th/Ts ratio and drug resistance mutations showed a diminished tumor response and higher NLR ratio exhibited a worse median PFS.