Abstract P014: Clinical impact of evaluating serum IgG fractions in advanced non-small cell lung cancer treated with immune checkpoint inhibitors
Authors: Oyanagi Jun , Koh Yasuhiro , Akiyama Yasuyuki , Morimoto Atsushi , Sato Koichi , Teraoka Shunsuke , Fujimoto Daichi , Tokudome Nahomi , Hayata Atsushi , Ozawa Yuichi , Akamatsu Hiroaki , Nakanishi Masanori , Ueda Hiroki , Yamamoto Nobuyuki 
Published: December 2021

Abstract
Background: Structure of N-linked glycan in immunoglobulin G (IgG) fragment crystallizable (Fc) region is associated with antigen-dependent cellular cytotoxicity (ADCC) activity. Although it has been known that N-glycan moiety is different between healthy individuals and cancer patients, the relationship between the N-glycan structure and treatment response in cancer patients is unknown. Here, we evaluated the putative ADCC activity by the N-glycan moiety of IgG-Fc using peripheral blood and analyzed its association with clinical benefits from immune checkpoint inhibitors (ICIs) in patients with advanced non-small cell lung cancer (NSCLC). Patients and Methods: Advanced NSCLC patients received nivolumab, pembrolizumab or atezolizumab treatment until disease progression or unacceptable toxicity. Serum samples were collected at baseline. Tumor responses were classified into complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD) based on RECIST v1.1. Durable clinical benefit (DCB) was defined as patients whose response was lasting over 6 months. Three IgG fractions (area 1, 2 and 3) corresponding to three peaks identified by affinity chromatography using TSKgel FcR-IIIA-NPR column (Tosoh, Japan) were quantified and the putative ADCC activity was estimated based on the ratio of area 3, which associates with highest ADCC activity, to the whole area. All statistical analyses were carried out using JMP Pro software (ver. 14.0). Mann-Whitney U-test was conducted. Time to event analysis was conducted using Kaplan-Meier methods and the log-rank test. Results: Ninety-seven patients were registered in the study between Jan 2016 and Nov 2018 at Wakayama Medical University. Characteristics of the patients were as follows: median age, 70 (range, 49-91); male. 78%; smoker, 79%; previous treatment ≥1, 77%; performance status 0-1, 82%; stage III/IV, 31/69%; squamous/non-squamous/unknown, 29/69/2%; nivolumab/pembrolizumab/atezolizumab, 46/42/12%. The objective response rate was 25.0% (24/96) and the disease control rate was 55.2% (53/96). The DCB rate was 45.4% (44/96). The median progression free survival (PFS) was 72 days (95%CI, 49 to 127) and median overall survival (OS) was 310 days (95% CI, 229 to 475). When time-to-event analysis was conducted by dividing into two groups at the median of the ratio of area 3 to the whole area, OS was significantly longer in patient with higher ratio than those with lower one in both entire cohort (median OS, 952 vs 482; 95% CI, 482 days-not reached and 233-744 days; log rank p=0.0292) and 2nd line cohort (median OS, 952 vs 292; 95% CI, 453 days-not reached and 120-692 days; log rank p=0.0010). Evaluation of IgG fraction was not associated with tumor response or PFS in this study cohort. Conclusion: Our results suggest that evaluation of the N-glycan moiety of IgG-Fc in peripheral blood has a potential as a prognostic biomarker in advanced NSCLC patients treated with ICIs.
Citation Format: Jun Oyanagi, Yasuhiro Koh, Yasuyuki Akiyama, Atsushi Morimoto, Koichi Sato, Shunsuke Teraoka, Daichi Fujimoto, Nahomi Tokudome, Atsushi Hayata, Yuichi Ozawa, Hiroaki Akamatsu, Masanori Nakanishi, Hiroki Ueda, Nobuyuki Yamamoto. Clinical impact of evaluating serum IgG fractions in advanced non-small cell lung cancer treated with immune checkpoint inhibitors [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2021 Oct 7-10. Philadelphia (PA): AACR; Mol Cancer Ther 2021;20(12 Suppl):Abstract nr P014.