What we mean when we talk about MRD in myeloma. A review of current methods. part 1 of a two-part series

Assessment of minimal residual disease (MRD) is becoming standard of care for potentially curable cancers, like some leukemias. For diseases not currently curable, like multiple myeloma (MM), the optimal methodology to assess MRD is much less clear, let alone the clinical significance. In this two-part series, we review each of these aspects of MRD in MM. In part 1, we review different methodologies available for MRD assessment, with an emphasis on multiparameter flow cytometry (MFC) and duplex immunohistochemistry. There is currently a strong push in the MM community for the use of MFC, based on studies demonstrating MRD negativity by MFC being associated with delayed time to relapse. After participating in a recent international meeting of leaders in the field, convened to discuss this topic, we review and assess the voiced opinions and published data. While great strides have been made toward the standardization of MFC for MRD, we review not only intrinsic biologic differences between MM and leukemia but also the technical challenges that follow from these differences, including the need for live cells, a difficult to characterize immunophenotype, and significant interlaboratory variability in MFC testing and interpretation.