接受 BCMA 靶向 CAR-T 治疗的复发/难治性多发性骨髓瘤患者中 BCMA 表达的动态变化

There is limited systemic data on the dynamics of BCMA-target antigen expression with BCMA CAR-T at relapse.

We analyzed 76 patients receiving standard-of-care BCMA-directed CAR-T who underwent real-time BCMA expression evaluation at baseline (n = 50), relapse (6), or both (20) using flow cytometry (FC) and/or immunohistochemistry (IHC). BCMA was universally expressed at baseline with significant heterogeneity in expression level. No concordance was seen between FC and IHC in categorizing high vs. low expression (Spearman: 0. 07, Cohen kappa: 0). Plasma cell BCMA expression by FC correlated with clinical outcomes, whereas IHC did not. High BCMA expression by FC was associated with increased likelihood for VGPR/CR (p = 0. 007) and longer time to progression (p = 0.

005), including the ciltacabtagene autoleucel cohort (median: 23. 0 vs. 7. 7 months, p = 0. 02). Relapsed patients retained BCMA expression by FC, though 29% (5/16) had BCMA loss by IHC, with 4/5 showing concurrent positive BCMA expression by FC. BCMA expression at relapse by FC was significantly lower than baseline (p = 0.

04); downregulation ( 25% decrease) occurred in 50% (8/16) with paired samples. Higher BCMA expression by FC correlated with higher likelihood of deep, durable responses following BCMA-directed CAR-T. While BCMA loss is rare, decreased expression is common at relapse, with implications for sequencing BCMA-directed therapies.