The effects of anti-PD-1 therapy on programmed death-ligand 1 expression and glucose metabolism of normal organs in patients with advanced non-small cell lung cancer.

Abstract

Objectives: To investigate how anti-PD-1 treatment affects both Programmed Death-Ligand 1 (PD-L1) expression and glucose metabolism within normal tissues of advanced non-small cell lung cancer (NSCLC) patients using a dual SPECT/CT and PET/CT imaging approach.

Methods: Ten advanced NSCLC patients (NCT04436406) undergoing anti-PD-1 therapy ± chemotherapy underwent imaging at baseline and 9 weeks. PD-L1 expression was measured using [^99mTc]-labelled single-domain PD-L1 antibody single-photon emission computed tomography/computed tomography ([^99mTc]NM-01 SPECT/CT). Glucose uptake was measured using [¹⁸F]-Fluorodeoxyglucose positron emission tomography/computed tomography ([¹⁸F]FDG PET/CT). Two independent observers marked regions of interest across normal organs (liver, lung, spleen, bone marrow, muscle, kidney, pancreas, left ventricular myocardium, and blood pool) to determine maximum and mean standardized uptake values (SUV) at both time points. Observer agreement was measured with an intraclass correlation coefficient (ICC).

Results: No significant changes in SUVs, indicating PD-L1 expression and glucose metabolism, were detected in normal organs after 9 weeks of treatment (all P > .05). No patients developed immune-related adverse events (irAEs) during the study period. Observer measurements showed excellent consistency with an ICC of 0.99 (95% confidence interval 0.99-0.99).

Conclusions: Our study showed stable PD-L1 expression and glucose metabolism within normal organs in advanced NSCLC patients treated with anti-PD-1 therapy ± chemotherapy. Interobserver reliability between observers was excellent. Additional studies with larger patient groups and a specific focus on irAE cases are needed.

Advances in knowledge: Through a dual-modality molecular imaging approach, this research provides novel insight into anti-PD-1 therapy's effects on PD-L1 expression and glucose metabolism in normal organs of NSCLC patients, demonstrating that these parameters remain stable post-treatment.