Applications of Multiparameter Flow Cytometry in the Diagnosis, Prognosis, and Monitoring of Multiple Myeloma Patients.

Multiple myeloma (MM) is one of the most common hematological malignancies and remains incurable. However, the survival of multiple myeloma patients has significantly increased due to the implementation of novel therapies along with autologous stem cell transplantation, changing the natural history of the disease. Consequently, there is an unmet need for more sensitive response assessment techniques capable of quantifying minimal tumor burden to identify patients at higher risk of early relapse. Multiparameter flow cytometry (MFC) is an essential tool for diagnosing and monitoring patients with various hematological conditions and has recently gained prominence in identifying, characterizing, and monitoring malignant plasma cells. The implementation of Next-Generation Flow (NGF) by EuroFlow aims to overcome the pitfalls of conventional MFC, including lack of standardization and lower sensitivity, by offering standardized and optimized protocols for evaluating response depth. Both MFC and NGF have wide-ranging applications in MM for diagnosis and measurable residual disease (MRD) monitoring. Plasma cell identification and clonality evaluation through MFC and NGF assist in diagnostic workup and are routinely used to assess therapeutic response through MRD analysis. Additionally, flow cytometry is applied for circulating tumor plasma cell (CTPC) enumeration, which has demonstrated significant prognostic value. Immune composition studies through MFC may provide better understanding of disease biology. Furthermore, MFC provides additional information about other bone marrow cell populations, assessing cellularity, immunophenotypic characteristics of plasma cells, and possible hemodilution. This review explores the applications of MFC and NGF in MM, highlighting their roles in diagnosis, response assessment, and prognosis. Beyond their established use in MRD monitoring, flow cytometry-derived immunophenotypic profiles show strong potential as cost-effective prognostic tools. We advocate for future studies to validate and integrate these markers into risk stratification models, complementing cytogenetic analyses and guiding individualized treatment strategies.