MM-167: Phenotypic and Prognostic Evaluation of Circulating Plasma Cells in Newly Diagnosed Multiple Myeloma Detected with Next-Generation Flow Cytometry (NGF)

Abstract

Context: The apparent heterogeneity of multiple myeloma (MM) necessitates the identification of novel biomarkers with a strong prognostic value. The presence of circulating plasma cells (CPCs) in newly diagnosed patients (NDMM) has been proposed as a valuable prognostic biomarker, though current methodologies reported yielded heterogeneous results due to variations in their detection efficacy. Objective: To evaluate the characteristics and prognostic value of CPCs, utilizing highly sensitive next-generation flow (NGF) cytometry, able to detect aberrant plasma cells (APCs) at levels reaching 10−6. Design, Patients, and Methods: Peripheral blood (PB) and matched bone marrow (BM) samples from 325 NDMM patients were prospectively evaluated for the presence of APCs according to Euroflow-NGF protocol for a median LOD reached of 3.6 × 10−6. CPC numbers correlated with various clinical parameters and the median follow-up period since CPC assessment was 24 months. Main outcome measures: Clinical outcome endpoints considered were the type of response to induction therapy and PFS. Our hypothesis was that higher CPC numbers would correlate with adverse prognostic features and worse clinical outcomes. Results: CPCs were detected in 288/325 (88.6%) samples (range, 0.0002% - 63.8% of PBNCs). CPCs and matched BM APCs had similar phenotypic characteristics; notably, when two or more phenotypically distinct APC-subsets were detectable in BM, the same subsets were also present in PB with similar relative frequency. Higher CPC numbers (>0.1% of PBNCs) correlated with increased BM infiltration, ISS-3 stage, and high-risk cytogenetics (p Conclusions: NGF enables the detection of rare CPCs in NDMM, many of which would have been falsely missed with a lower sensitivity approach. The similarity of CPCs with BM APCs and the strong correlation of higher CPC numbers with adverse disease characteristics highlight a valuable surrogate prognostic tool, which could representatively replace standard BM invasive methods.