Abstract 5579: Single cell characterization of circulating plasma cells and BCMA levels in patients with multiple myeloma

Multiple myeloma (MM), a disease caused by the clonal proliferation of plasma cells (PCs), is the second leading hematologic malignancy in the world, with a global incidence rate increase of 126% and mortality rate increasing by 94% in the past decade. Recently, B cell maturation antigen (BCMA) has emerged as a promising biomarker and therapeutic target for MM due to its selective high expression on malignant PCs, improving the treatment landscape. However, the current diagnostic workup relies on bone marrow aspirates (BMA) which are highly invasive and do not allow for the detection of BCMA levels on circulating PCs, severely limiting the options for repeatable assessments and treatment-monitoring. In our study, we report the utility of a blood-based liquid biopsy, using enrichment-free high definition single cell assay (HDSCA) for the detection, quantification, and morphological characterization of circulating PCs and other BCMA+ cells. We applied a previously validated 4-color immunofluorescence assay using DAPI, CD138, BCMA, and CD45 to examine matched peripheral blood and BMAs from 68 patients across the MM disease spectrum (11 monoclonal gammopathy of undetermined significance [MGUS], 21 smoldering MM [SMM], 18 newly diagnosed MM, and 18 relapsed refractory MM [RRMM]) and peripheral blood from 23 normal donors as controls. Our analysis revealed diverse subtypes of circulating CD138(+/-), BCMA(+/-), and CD45(+/-) cells across the patients, representing both normal and abnormal PCs. We detected significantly higher circulating CD138+ BCMA(+/-) cells in MM precursor conditions (MGUS, SMM), compared to the normal donors. Additionally, we were able to detect BCMA+ oncosomes (identified by the lack of a nuclear structure) in the circulation of patients from both precursor and overt disease conditions. Our findings establish the utility of HDSCA blood-based liquid biopsy for early disease detection and anti-BCMA therapy response monitoring in MM and other B-cell malignancies expressing BCMA. Citation Format: Sonia Maryam Setayesh, Stephanie Shishido, Libere Ndacayisaba, Amin Naghdloo, Jeremy Mason, Dean Tessone, Carli Kaleta, Robert Z. Orlowski, Elisabet E. Manasanch, James Hicks, Peter Kuhn. Single cell characterization of circulating plasma cells and BCMA levels in patients with multiple myeloma. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5579.