Absolute Lymphocyte Count after BCMA CAR-T Therapy is a Predictor of Response and Outcomes in Relapsed Multiple Myeloma

• Maximum ALC (ALCmax) in the first 15 days after BCMA CAR-T cell infusion is associated with deeper response and occurrence of CRS and ICANS.

• ALCmax less than 0.5 x103/uL is predictive of non-responders, while that >1.0 is an independent prognostic biomarker for sustained response.

BCMA-targeting CAR-T cells used in multiple myeloma (MM) are rapidly becoming a mainstay in the treatment of relapsed/refractory (RR) disease, and CAR-T cell expansion post-infusion has been shown to inform depth and duration of response, but measuring this process remains investigational. This multicenter study describes the kinetics and prognostic impact of absolute lymphocyte count (ALC) in the first 15 days after CAR-T infusion in 156 relapsed MM patients treated with the BCMA-targeting agents cilta-cel and ide-cel. Patients with higher maximum ALC (ALCmax) had better depth of response, progression-free survival (PFS), and duration of response (DoR). Patients with ALCmax >1.0 x103/uL had a superior PFS (30.5 versus 6 months, p <0.001) compared to those ≤1.0x103/uL, while patients with ALCmax ≤0.5 x103/uL represent a high-risk group with early disease progression and short PFS (HR 3.4, 95 CI: 2 -5.8, P <0.001). In multivariate analysis, ALCmax >1.0 x103/uL and non-paraskeletal extramedullary disease were the only independent predictors of PFS and DoR after accounting for ISS staging, age, CAR-T product, high-risk cytogenetics and number of previous lines. Moreover, our flow cytometry data suggests that ALC is a surrogate for BCMA CAR-T expansion and can be used as an accessible prognostic marker. We report for the first time the association of ALC after BCMA CAR-T infusion with clinical outcomes and its utility in predicting response in RRMM patients.