Abstract 7630: Therapeutic relevance of systemic immune status to treatment effects of abemaciclib

Abstract Background: The addition of a CDK4/6 inhibitor (CDK4/6i) on endocrine therapies (ET) has been currently a standard treatment for hormone receptor (HR)-positive HER2-negative metastatic breast cancers (MBCs). Especially abemaciclib has been implicated in multiple mechanisms of action including cell cycle arrest, senescence. In addition, immunomodulatory effects have been suggested but are not yet clear. The aim of the study was to investigate the clinical relevance of abemaciclib to systemic immune status by examining the status of peripheral immune cells in patients with MBC who received abemaciclib plus ET. Methods: Patients with MBC who were treated with abemaciclib plus ET in our hospital were included in this study. Response was evaluated by RECIST 1.1. Peripheral blood at the initiation of abemaciclib treatment, 4 weeks, 12 weeks and 24weeks after abemaciclib treatment initiation were analyzed using mass cytometry by time of flight (CyTOF). Changes of cellular densities of each immune cell and survival by immune cell density were analyzed without calculating p values because of small sample number. Results: Twenty patients were enrolled, among whom 14 and 6 received an aromatase inhibitor and fulvestrant, respectively, as concomitant ET. 7 premenopausal patients received an LH-RH analogue. The analysis of serial blood collection showed an increase in CD8-positive T cell density by 12.5% and conversely a decrease in monocyte density by 52.3% at 4 weeks after treatment initiation. In responders (N = 10), an increase of the ratio between CD8-positive T cell density and Treg density (CD8/Treg) at 4 weeks after the treatment initiation were observed (65.2%), while not in non-responders (7.3%). In the analysis of the blood samples at the treatment initiation, lower Treg density and lower NK density at treatment initiation indicated longer PFS than the counterparts (median PFS for Treg: low, not reached; high, 8.8 months; for NK: low, not reached; high, 8.8 months). Conclusion: An increase of CD8/Treg at 4 weeks after the treatment initiation was associated with a good response in patients with HR-positive HER2-negative MBC treated with abemaciclib plus ET. Our results suggest an association between systemic immune status and clinical outcome in MBC patients who received abemaciclib plus ET treatment. A larger study is needed to validate the results. Citation Format: Takayuki Ueno, Shigehisa Kitano, Takayuki Kobayashi, Makiko Yamashita, Fumikata Hara, Yukinori Ozaki, Meiko Nishimura, Toshimi Takano, Naoko Toriguchi, Tsutomu Kawaguchi. Therapeutic relevance of systemic immune status to treatment effects of abemaciclib [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7630.