Multiple myeloma (MM) is the second most common hematologic malignancy. It is still largely incurable, but treatment has changed greatly with proteasome inhibitors, immunomodulatory drugs, monoclonal and bispecific antibodies, autologous stem cell transplantation and chimeric antigen receptor T cells. Most patients now achieve a complete response. As a result, conventional criteria, based on monoclonal protein, serum free light chains and bone marrow plasma cell counts, can no longer distinguish different depths of response. Measurable residual disease (MRD) has therefore become the reference endpoint. The International Myeloma Working Group defines MRD negativity as the absence of clonal plasma cells among at least 100,000 bone marrow cells. MRD negativity predicts progression-free and overall survival, independently of cytogenetic risk and disease stage. The US Food and Drug Administration has also accepted it as an early endpoint for accelerated approval. This review examines the three main technologies now used to assess MRD in MM. Next-generation flow cytometry is standardized through the EuroFlow two-tube, eight-color protocol. It gives same-day results and can be applied to all patients without a baseline sample. Next-generation sequencing of clonal immunoglobulin gene rearrangements is more sensitive and can be used on stored samples. It can also follow clonal evolution and the appearance of resistance mutations. Mass spectrometry is performed on peripheral blood. It detects the patient-specific clonotypic immunoglobulin with much higher sensitivity than electrophoretic methods and allows frequent, minimally invasive monitoring. For now, however, it complements marrow-based testing and does not replace it. For each method, we discuss analytical principles, sensitivity, standardization, pre-analytical requirements, clinical validation and limitations, and we briefly consider the growing contribution of artificial intelligence. The review also covers the role of cytogenetics and fluorescence in situ hybridization in baseline risk assessment. Finally, we discuss the limits of MRD testing in a disease that is often unevenly distributed between marrow, extramedullary sites and peripheral blood. Current evidence suggests that combining marrow-based and blood-based assays may identify residual disease most accurately. This combined approach has not yet been validated prospectively, and for now it should be used within clinical trials.

Background: Interpreting low-grade of high-sensitivity cardiac troponin I (hs-TnI) concentrations reflecting myocardial injury in asymptomatic populations remains clinically uncertain. This study characterized predefined sex-specific hs-TnI categories in apparently healthy blood donors and compared them with conventional cardiovascular assessment methods. Methods: We performed a cross-sectional analysis of 292 blood donors (77 women, 26.4%; 215 men, 73.6%; age range, 40–65 years). Hs-TnI was measured using the Abbott ARCHITECT STAT High Sensitive Troponin-I assay and categorized according to predefined sex-specific thresholds. Categories were compared with clinical variables, cholesterol/HDL-ratio categories, Framingham Risk Score categories, and SCORE2 in eligible participants (n = 287). Additional analyses included non-parametric comparisons, Spearman correlations, agreement statistics, and multivariable models. A sensitivity analysis used sex-specific empirical hs-TnI tertiles, and effect sizes with bootstrap 95% confidence intervals were reported for key comparisons. Results: Hs-TnI categories were low in 253 subjects (86.6%), intermediate in 17 (5.8%), and elevated in 22 (7.5%). Hs-TnI was markedly skewed, especially in the elevated category (median, 21.5 ng/L; IQR, 15.25–36.0; range, 11–199). Agreement with conventional categories was low, with weighted kappa values of 0.035 versus Framingham, −0.008 versus cholesterol/HDL-ratio categories, and 0.076 versus SCORE2. Conventional cardiovascular variables showed limited independent association with intermediate/elevated hs-TnI categories. Tertile-based sensitivity analyses yielded weighted kappa values of 0.045 versus Framingham, 0.033 versus cholesterol/HDL-ratio categories, and 0.037 versus SCORE2. Conclusions: In selected blood donors, predefined hs-TnI categories showed limited concordance with conventional cardiovascular scores, exploratory-wise suggesting a distinct phenotype of low-grade myocardial injury.