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<p>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 (<i>n</i> = 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 (<i>p</i> = 0.007) and longer time to progression (<i>p</i> = 0.005), including the ciltacabtagene autoleucel cohort (median: 23.0 vs. 7.7 months, <i>p</i> = 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 (<i>p</i> = 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.</p><p></p>

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Dynamics of BCMA expression in patients with relapsed/refractory multiple myeloma receiving BCMA-directed CAR-T therapy

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月4日

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  • Masooma Shifa Rana,
  • Sebastian Fernandez-Pol,
  • Alexandria Jensen,
  • Vanna Hovanky,
  • Arash Velayati,
  • Jean S. Oak,
  • Oscar Silva,
  • Erik Ames,
  • Lori S. Muffly,
  • Bita Sahaf,
  • Sally Arai,
  • Vanessa E. Kennedy,
  • Sushma Bharadwaj,
  • David J. Iberri,
  • Michaela Liedtke,
  • Yasodha Natkunam,
  • Parveen Shiraz,
  • Wen-Kai Weng,
  • Melody Smith,
  • Matthew J. Frank,
  • Crystal L. Mackall,
  • Saurabh Dahiya,
  • Lekha Mikkilineni,
  • David B. Miklos,
  • Hitomi Hosoya,
  • Surbhi Sidana

摘要

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.