Abstract B38: Immunologic monitoring markers of clinical responses to anti-PD-1 therapy for non-small cell lung cancer
Authors: Oka Mikio , Kurose Koji , Ohue Yoshihiro , Karasaki Takahiro , Futami Junichiro , Masuda Takeshi , Fukuda Masaaki , Kinoshita Akitoshi , Shimizu Katsuhiko , Nakata Masao , Hattori Noboru , Yamaguchi Hiroyuki , Fukuda Minoru , Oga Toru , Kakimi Kazuhiro 
Published: March 2020

Abstract
Background: Programmed cell death-1 (PD-1) and PD-ligand1 (PD-L1) inhibitors effectively treat advanced non-small cell lung cancer (NSCLC) and prolong patient survival, resulting in standard therapies of NSCLC. Clinical benefits of good response and long survival with anti-PD-1/L1 therapy are limited in a small population of NSCLC patients, although combinations with chemotherapy have been extensively developed. Tumor PD-L1 expression and mutation burden are well known as response biomarkers for these therapies. On the other hand, biomarkers monitoring clinical responses during anti-PD-1/L1 therapy have yet to be identified. Very recently, we reported robust biomarkers of NY-ESO-1 and XAGE1 serum antibodies (Abs) predicting clinical benefits with anti-PD-1 monotherapy for NSCLC. NY-ESO-1 and XAGE1 are major cancer-testis antigens in NSCLC and play important roles in the immune surveillance. Then, we investigated whether these Abs became monitoring markers of clinical responses to anti-PD-1 monotherapy in NSCLC.
Patients and Methods: Patient sera were serially obtained during anti-PD-1 therapy (nivolumab or pembrolizumab) of the first or later line as a standard care, and serum Abs against NY-ESO-1 and XAGE1 antigens and mutant p53 (as neoantigen) were detected by ELISA. Ab-positive was defined for serum with extrapolated titers exceeding or equal to 100 (≥100). Objective responses to anti-PD-1 therapy were assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1.
Results: In patients responding to anti-PD-1 therapy, NY-ESO-1/XAGE1 serum Ab titers were increased with several spikes within two to three months after therapy and were gradually decreased with tumor shrinkage. The increase of Ab titers showed rapid or gradual type, and the former reflected rapid tumor shrinkage and the latter did slow one. The Ab titers in patients with complete response (CR) were gradually decreased to an undetectable level, and these patients experienced no recurrence. However, the decreased titers in patients with partial response (PR) remained plateau or under 100, and some of these patients experienced recurrence or regrowth. The Ab titers in patients with progressive disease (PD) were gradually increased and not decreased. On the other hand, p53 serum Ab titers were gradually increased after the peaks of NY-ESO-1/XAGE1 serum Ab titers, suggesting antigen-spreading of neoantigens associated with tumor destruction.
Conclusions: Our results suggest that NY-ESO-1 and/or XAGE1 serum Abs are robust monitoring biomarkers of clinical responses to immune checkpoint inhibitors and are useful for decision making regarding the continuation or discontinuation of therapy in clinical settings.
Citation Format: Mikio Oka, Koji Kurose, Yoshihiro Ohue, Takahiro Karasaki, Junichiro Futami, Takeshi Masuda, Masaaki Fukuda, Akitoshi Kinoshita, Katsuhiko Shimizu, Masao Nakata, Noboru Hattori, Hiroyuki Yamaguchi, Minoru Fukuda, Toru Oga, Kazuhiro Kakimi. Immunologic monitoring markers of clinical responses to anti-PD-1 therapy for non-small cell lung cancer [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2019 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(3 Suppl):Abstract nr B38.