LAUSR

For many decades, international collaborative efforts have driven therapeutic advances in multiple myeloma (MM). The establishment of uniform response criteria by the International Myeloma Working Group (IMWG) has been pivotal for this progress, as adherence to strict definitions ensures data comparability between trials. An essential prerequisite for the use of uniform criteria is the application of standardized methods. Of particular interest herein is the assessment of minimal residual disease (MRD) by multiparametric flow cytometry (MFC). This has been incorporated into the IMWG response criteria since 2011 to enable better risk stratification of a growing number of patients reaching a complete remission and has the promise to be used both as a surrogate marker for overall and progression-free survival and to inform treatment decisions. However, in contrast to most routine diagnostic tests for response assessment in MM, this assay has until recently suffered from large interlaboratory variations in terms of sample processing and data acquisition, resulting in highly heterogeneous sensitivities. To enable uniform and sensitive MFC MRD assessment between laboratories, EuroFlow has developed standardized operating procedures. Their next-generation flow method has been incorporated as the gold standard for MFC MRD measurements in the latest IMWG response criteria, which is expected to greatly improve data validity and comparability. Even though the establishment of standardized protocols has been an important step towards achieving uniform MFC MRD assessment in MM, the usefulness of these protocols depends heavily on their successful implementation in a wide range of laboratories. This is of particular relevance for international clinical trials that depend on a collaborative effort of multiple reference laboratories for timely MRD assessment, irrespective of geographical location of sampling. Nevertheless, it remains largely unknown whether fully standardized multi-laboratory MM MFC MRD assessment can be achieved in such a setting. To investigate this, a novel quality assurance (QA) program was established in 2016 within the framework of the European Myeloma Network (EMN): the EMN MRD QA program. This program aims to assess the validity and comparability of MFC MRD measurements within and between EMN trials by distributing fresh MM bone marrow and peripheral blood samples and complements existing QA programs led by EuroFlow using peripheral blood samples from healthy donors or raw data files from MM MFC MRD measurements. Data obtained within the EMN MRD QA program show that it is feasible to fully standardize MFC MRD assessment between laboratories, resulting in a high concordance over the entire range of detectable MRD levels. Participation in QA programs is essential to ensure complete interlaboratory standardization without compro-