Abstract 2101: Absolute lymphocyte count after CAR-T therapy has different kinetics and predicts better outcomes in B-cell malignancies

Abstract Introduction: Chimeric antigen receptor (CAR) T-cell therapy targeting CD19 and BCMA antigens are now a valuable option for patients with relapsed or refractory (R/R) B-Cell malignancies Commercially available products consist of an antigen binding domain against CD19 or BCMA and one of two main co-stimulatory molecules, CD28 (Axi-Cel , Brexu-Cel ) and 41-BB (Tisa-Cel, Liso-Cel, Cilta-cel, and Ide-cel). In this analysis, we studied the prognostic impact of absolute lymphocyte count (ALC) in patients with B-Cell malignancies treated with CAR-T therapy and investigated the differences in ALC kinetics between the products and co-stimulatory molecules. Methods: We analyzed data from patients with R/R B-Cell malignancies treated with CAR-T therapy from 2017 to 2024 at our institutions. All relevant baseline characteristics were collected. ALCmax was defined as the highest ALC from day 0 through 15, not attributable to leukemic disease. The ALC values and kinetics were compared among products and co-stimulatory molecules. Survival and Cox proportional hazards analyses were performed with PFS as an outcome. Results: We identified 245 patients with B cell malignancies (DLBCL, MCL, FL, CLL, and MM). The most common malignancy was DLBCL (62%) followed by MM (26%). Most used product was Axi-cel 119 (49%) in the lymphoma cohort in comparison to cilta-cel in the MM cohort. ALCmax was significantly higher in Liso-Cel and Tisa-Cel compared with Axi-cel and Brexu-Cel treated patients (p < 0.001). ALCmax was also higher in CD19 and BCMA 4-1BB CAR- T products compared to CD19-CD28 products (0.76 vs 1.28 vs 0.59 x 103/uL, respectively) (p < 0.001). In Univariate analysis of DLBCL patients treated with any of the CD19 CAR-T products, higher ALCmax was associated with improved PFS (HR: 0.71, CI: 0.5- 0.9), while an ALCmax < 0.5 x 103/uL was associated with worse PFS (Hazard ratio (HR) 2.2, CI 1.13 - 3.18). This ALCmax cutoff was still associated with worse PFS in CD19 CAR-T products with either CD28 or 41-BB co-stimulatory molecules. Similarly, ALCmax was associated with better PFS after accounting for lines of therapy and high-risk cytogenetics in MM patients treated with the BCMA CAR-T products (HR: 0.42, CI: 0.26 - 0.78, p = 0.001). In the DLBCL cohort, ALCmax < 0.5 x 103/uL and high LDH were independent risk factors of worse PFS after accounting for age, stage, ferritin levels. Flow cytometry data showed the ALCmax was positively correlated with CAR-T cells expansion in both MM and DLBCL. Conclusions: ALCmax was associated with better PFS in DLBCL patients treated with both types of CD19 products and in MM patients treated with BCMA-41-BB CAR-T products. This data suggests that ALCmax is a good marker for response to CAR-T therapy and encourages better understanding of the factors influencing ALC levels between the CAR-T products and disease subtypes. Citation Format: Juan Esteban Velez-Hernandez, Theresia Akhlagi, Caitlin Unkenholz, Juan Harvey Martinez, Juan Jose Fernandez-Rengifo, Christian A. Gordillo, Hei Ton Chan, Markus Mapara, Giorgio Inghirami, Ran Reshef, Samuel Yamshon, Mateo Mejia Saldarriaga, Mark Bustoros. Absolute lymphocyte count after CAR-T therapy has different kinetics and predicts better outcomes in B-cell malignancies [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 2101.