B-cell maturation antigen (BCMA) immunohistochemistry (IHC) staining in multiple myeloma (MM) patients with prior use of BCMA-based therapies.

Abstract

e19540 Background: BCMA is a critical therapeutic target in multiple myeloma (MM), but resistance to BCMA-based therapies can occur due to altered BCMA expression, limiting treatment efficacy. Immunohistochemical (IHC) staining of BCMA in patients with prior BCMA-based therapies is essential for detecting changes in expression, which may reflect resistance mechanisms and guide future treatment decisions. This approach aids in identifying patients who may not benefit from further BCMA-targeted therapies and provides valuable insights into tumor biology and therapeutic resistance. Methods: We identified MM patients who had undergone BCMA IHC staining at the University of Arkansas for Medical Sciences up until January 1st, 2025. BCMA expression was evaluated in central lab by assessing its membranous and/or cytoplasmic localization in neoplastic plasma cells. Clinical data, including survival outcomes and the sequence of MM therapies, were analyzed to correlate BCMA expression with treatment response and resistance patterns. Cellular positivity is scored as follows: 0 indicates no positive cells (negative); 1 reflects <1% positive cells (rare); 2 represents 1-25% positive cells (focal); 3 denotes 26-75% positive cells (variable); and 4 indicates >75% positive cells (uniform). Results: A total of 23 patients underwent BCMA IHC testing during the study period. Of these, 61% were male and 13% were Black. The median age was 57 years (range 42-72 years), and 22% had an Eastern Cooperative Oncology Group (ECOG) performance status of ≥2. Patients had a median of 6 prior lines of therapy (range, 2-18) before BCMA IHC testing. Prior BCMA-based therapy was used in 87% of patients, with Blenatmamab mafoditin used in 22%, teclistimab in 70%, BCMA-based CAR-T in 52%, and more than one BCMA-based therapy in 48%. BCMA IHC results showed that 40% of patients had no positive cells (score 0), 15% had rare positivity (<1%, score 1), and 45% had variable or focal positivity (scores 2–4). In contrast, all three patients without prior BCMA therapy were positive for BCMA expression. Among patients with negative BCMA staining, one treated with teclistimab showed no response, while the others were treated with alternative therapies, including talquetamab. Conclusions: BCMA expression can be significantly reduced or absent in MM patients who have received prior BCMA-based therapies, suggesting a mechanism of resistance. Routine BCMA IHC testing maybe needed before initiating additional BCMA-targeted therapies to better guide treatment decisions. Notably, patients without prior BCMA exposure retain BCMA expression, indicating potential benefit from BCMA-targeted therapies in this group.