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    Cellular and T cell engager Immunotherapy

    Monitoring of anti-BCMA CAR-T cells and non-CAR-T immune subsets in multiple myeloma patients

    P-092: Monitoring of anti-BCMA CAR-T cells and non-CAR-T immune subsets in multiple myeloma patients

    Wednesday, September 25, 2024

    • Ondrej Venglar, PhD

      Postdoctoral researcher
      Department of Hematooncology, University Hospital Ostrava
      Ostrava, Czech Republic

    Introduction: Chimeric antigen receptor (CAR) T cells targeting B-cell maturation antigen (BCMA) represent a groundbreaking therapeutic option for multiple myeloma (MM). Monitoring CAR-T cell expansion might play a role in the prediction of treatment efficacy and the severity of side effects

    Methods: Peripheral blood (PB) samples (n = 73) from 12 MM patients in total were assessed at various timepoints starting at day 0 (D0)/day of infusion or D2, with resampling at D7, D10, D14, D21, D28 and M1-M6 each month. An 8-color flow cytometry panel (CD3, CD4, CD8, CD19, CD20, CD45, CD16+CD56, BCMA CAR) using dried reagent tubes was utilized to assess levels of BCMA CAR-T cells and other immune subsets.

    Results: Median number of assessed CD45+ leukocytes was 164 x 103 with median limit of detection 0.0122%. The presence of CAR-T cells was first detectable at D7 (median count/µl PB, min-max: 9, 0.55-2152) with maximum expansion at D10 (966, 222-11924). From D14 (937, 219-2800), the CAR-T cell counts gradually dropped to detectable levels in 3/5 patients at M1-2 and 1/4 patients at M2-3 (Figure 1). The CD4/CD8 ratio significantly decreased over time from D7 to D28 in the CAR-T cell compartment (median percentage in CAR-T fraction: CD4+, D7 = 74.20% vs. D28 = 54.08%, p = 0.0079; CD8+, D7 = 17.50% vs. D28 = 44.89%, p = 0.0016). A similar shift in the CD4/CD8 ratio was also observed in non‑CAR T cells between D0 and M5-6. B cells were completely depleted from D7 to D28 with their first considerable reappearance in circulation at M1-2 in 3/5 patients. The monocyte percentage in the leukocyte fraction significantly increased from D2 to D7 (median: D2 = 2.15% vs. D7 = 25.60%, p = 0.0028). NK cell levels in the lymphocyte fraction were not significantly affected by the therapy in any of the timepoints.

    Conclusions: The data obtained from this multicentric collaboration describe the dynamics of CAR-T cell expansion as well as of non-CAR-T immune subsets