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