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    Cellular and T cell engager Immunotherapy

    Category: Cellular and T cell engager Immunotherapy

    Kinetic Characteristics of T Cells in CAR-T Therapy for Multiple Myeloma: A Real-World Analysis

    (PA-066) Kinetic Characteristics of T Cells in CAR-T Therapy for Multiple Myeloma: A Real-World Analysis

    Friday, September 19, 2025

    • Cai zhen, Professor

      Chief Physician
      The First Affiliated Hospital, Zhejiang University School of Medicine


    Introduction:      Chimeric Antigen Receptor T-cell (CAR-T) therapy has shown remarkable efficacy in treating hematologic malignancies in recent years. However, the long-term functional dynamics, mechanisms of exhaustion, and impact on the immune microenvironment of CAR-T cells remain insufficiently explored, particularly in real-world settings. This multicenter study investigates the kinetic profiles of T cells in patients with multiple myeloma treated with a fully human CAR-T cell therapy, equecabtagene autoleucel. We focus on the temporal evolution of differentiation subsets, exhaustion markers, and senescence phenotypes to provide a theoretical foundation for optimizing CAR-T therapy strategies.

    Methods:   

    This study included patients receiving eque-cel infusion at the First Affiliated Hospital of Zhejiang University and other centers from August 2023 to April 2025. Post-infusion CAR-T cell proportion, exhaustion, and senescence were assessed in subsets of patients. Differentiation subsets (central and effector memory) were analyzed among CD4+ and CD8+ CAR-T cells. Immune checkpoint expression (PD-1, TIGIT, TIM-3, LAG-3) and senescence markers (CD27−, CD28−, CD57+) were measured. Linear regression assessed associations between indices and time, reporting β coefficients, P-values, and adjusted R². Nonlinear trends were evaluated using generalized additive models, with significance set at P< 0.05.

    Results:   

    Of 30 patients, 40% were male (12/30), median age was 62 years (range: 49–77), 67% had IgG-type myeloma, 50% had high-risk cytogenetics, and 53% had extramedullary disease. Median follow-up was 161 days (range: 12–507). Data included multiple time points for senescence, exhaustion, and differentiation analysis (total 6,814 entries)，with over 80% collected within 50 days post-infusion. CAR-T persistence reached 391 days.
    Significant temporal trends (P< 0.05) were observed in most parameters. Notably, CD27    −CD8+ CAR-T proportions remained stable (P=0.766), whereas endogenous CD27−CD8+ T cells increased (P=0.004), suggesting engineered CAR-Ts sustain vitality while endogenous T cells are more prone to senescence. Differentiation analysis revealed endogenous effector memory CD8+ T cells expanded early but declined over time, while central memory CD8+ CAR-T cells increased at later stages. Exhaustion markers, especially PD-1, showed an initial rise then decline in both CAR-T and endogenous T cells. In contrast, TIGIT and TIM-3 expression did not change significantly, possibly due to limited late-stage samples.

     

    Conclusions:   

    This study sheds light on the dynamic evolution of T cells following CAR-T cell infusion in patients with multiple myeloma, offering valuable insights for refining CAR-T therapy strategies. However, further validation of differences across analytical models is required. Expanding the sample size and extending follow-up duration are essential to confirm these findings and enhance their clinical relevance.