MRD in multiple myeloma: Moving from "minimal" to "measurable"
Raffaella Cassano Cassano1, Rahul Banerjee2, Aimaz Afrough3
1University of Washington, Fred Hutchinson Cancer Center, Seattle, WA, USA; University of Pisa, Pisa, Italy; University of Foggia, Foggia, Italy.
Abstract:
The assessment of minimal residual disease (MRD) is an important prognostic factor in hematologic malignancies, including multiple myeloma (MM). Historically defined as cancer cells undetectable by conventional morphology, MRD is now more appropriately termed measurable residual disease, reflecting its quantitative and clinically actionable nature. Advances in next-generation flow cytometry and next-generation sequencing have enabled detection of disease at sensitivities as low as 10-6 and even 10-7, redefining the concept of complete response. Nonetheless, challenges remain regarding assay sensitivity, standardization, and interpretation of results. Achieving MRD-negativity is a strong and independent predictor of improved survival outcomes in both newly diagnosed and relapsed/refractory MM. Consequently, MRD negativity has increasingly been accepted by regulatory agencies as an intermediate endpoint supporting accelerated drug approval. This review summarizes MRD detection methodologies, clinically relevant thresholds, and therapeutic implications, highlighting the paradigm shift from "minimal" to measurable residual disease.
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