Abstract 7162: Association between circulating B cell subtypes and treatment response in patients with metastatic renal cell carcinoma (mRCC)
Authors: Zeynep B. Zengin, Marice Alcantara, Hedyeh Ebrahimi, Luis Meza, Nazli Dizman, Christian Nenninger, Jeremy Hall, Regina Barragan-Carrillo, Joann Hsu, Daniella Castro, Benjamin Mercier, Miguel Zugman, Salvador Jaime-Casas, Alex Chehrazi-Raffle, Abhishek Tripathi, Peter Lee, Motomichi Takahashi, Tanya B. Dorff, Marcin Kortylewski, Sumanta K. Pal
Journal: Cancer Research (2025)

Abstract Background: While immune checkpoint blockade (ICB) has transformed the treatment of mRCC, response rates remain suboptimal. Most studies of ICB in cancer have focused on T cells as mediators of antitumor responses, but recent evidence highlights B cells' role in modulating ICB efficacy. CD5+ B cells, a small subset with potential immunosuppressive properties, may contribute to immune evasion through mechanisms such as IL-6/STAT3 signaling. This study investigates the prognostic significance of circulating CD5+ B cells in mRCC patients (pts) treated with cabozantinib/nivolumab with or without CBM588, a live bacterial product. Methods: This open-label, randomized trial enrolled pts aged ≥18 years with histologically verified advanced or mRCC who had not received prior systemic therapy for metastatic disease. Pts were randomized in a 1:2 ratio to receive either cabozantinib/nivolumab alone (control arm) or in combination with CBM588 (experimental arm). Peripheral blood samples were prospectively collected at baseline and week 13. Samples were incubated with matched patients’ sera, diluted to 50% in culture media at 37°C with 5% CO2 for a minimum of 2 hours prior to immunostaining of surface markers, phospho-STAT3, and spectral cytometric analysis using the Cytek Aurora system. A two-sided Wilcoxon and two-sided Mann-Whitney U tests were used to compare B cells levels at the two prespecified time points and between the two arms, respectively. Progression-free survival (PFS) was estimated using the Kaplan-Meier method. Result: In total, 30 pts (20 male, 10 female) with mRCC were randomized to the control arm (10 pts) or the experimental arm (20 pts). The objective response rate in the control arm was 20%, compared to 79% in the experimental arm (p=0.004). The median PFS in the control arm was 13.4 months and was not reached in the experimental arm at the data cut-off (June 1, 2024; median follow-up: 25.8 months). Of the 30 pts, 27 had evaluable blood samples for the final analysis (8 pts in the control arm and 19 pts in the experimental arm). Pts with &amp;lt;75% CD5+ B cells at baseline (n=13) had a median PFS that was not reached, compared to 13.4 months in those with ≥75% CD5+ B cells (n=14 pts; p&amp;lt;0.01, HR=6.47, 95% CI: 1.40-29.88). Of note, CD5+ B cell levels did not differ significantly at baseline between treatment arms (p=0.43). Additionally, no significant difference in circulating CD5+ B cell levels was observed between baseline and week 13 in either arm (p&amp;gt;0.99 in the control arm vs. p=0.25 in the experimental arm). Conclusions: High baseline levels of CD5+ B cells are associated with inferior outcomes in patients with mRCC treated with cabozantinib and nivolumab. These findings suggest that CD5+ B cells may serve as a prognostic biomarker and a potential target to improve ICB outcomes in mRCC. Citation Format: Zeynep B. Zengin, Marice Alcantara, Hedyeh Ebrahimi, Luis Meza, Nazli Dizman, Christian Nenninger, Jeremy Hall, Regina Barragan-Carrillo, Joann Hsu, Daniella Castro, Benjamin Mercier, Miguel Zugman, Salvador Jaime-Casas, Alex Chehrazi-Raffle, Abhishek Tripathi, Peter Lee, Motomichi Takahashi, Tanya B. Dorff, Marcin Kortylewski, Sumanta K. Pal. Association between circulating B cell subtypes and treatment response in patients with metastatic renal cell carcinoma (mRCC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 7162.