{ "abstract": "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.", "abstract_shown": true, "affiliations": [ "Unit of Clinical Pathology, Santa Maria Goretti Hospital, 04100 Latina, Italy", "Unità Operativa Complessa Ematologia con Trapianto, Santa Maria Goretti Hospital, 04100 Latina, Italy", "Clinical Pathology Unit and Cancer Biobank, Department of Research and Advanced Technologies, Regina Elena National Cancer Institute—Istituto di Ricovero e Cura a Carattere Scientifico (I.R.C.C.S.), 00144 Rome, Italy", "Struttura Complessa Interaziendale Laboratorio Analisi Chimico Cliniche e Microbiologiche—Azienda Ospedaliera Santa Croce e Carle, 12100 Cuneo, Italy", "Dipartimento di Medicina e Chirurgia Traslazionale, Sezione di Patologia Generale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy", "Fondazione Policlinico Universitario “A. Gemelli”—Istituto di Ricovero e Cura a Carattere Scientifico (I.R.C.C.S.), 00168 Rome, Italy", "Unità Operativa Complessa-Medicina Trasfusionale, Santa Maria Goretti Hospital, 04100 Latina, Italy", "Dipartimento di Medicina Traslazionale e Medicina di Precisione, La Sapienza Università di Roma, 00185 Rome, Italy", "Unità Operativa Complessa-Ematologia, Ospedale S. Maria Goretti, 04100 Latina, Italy" ], "article_type": null, "arxiv": null, "author_total": 10, "authors": [ { "affs": [ 0 ], "name": "Sara Tartaglione", "orcid": "0000-0003-0934-4064" }, { "affs": [ 0 ], "name": "Marzia Tagliaferro" }, { "affs": [ 1 ], "name": "Maria Cristina Scerpa" }, { "affs": [ 2 ], "name": "Valerio Basile", "orcid": "0000-0002-9716-070X" }, { "affs": [ 0 ], "name": "Francesca D’Ambrosio", "orcid": "0000-0002-9629-4749" }, { "affs": [ 3 ], "name": "Patrizia Natali" }, { "affs": [ 4, 5 ], "name": "Mariapaola Marino", "orcid": "0000-0001-9155-6378" }, { "affs": [ 6 ], "name": "Francesco Equitani", "orcid": "0000-0001-5400-4996" }, { "affs": [ 7, 8 ], "name": "Luca Maurillo", "orcid": "0000-0001-7297-4988" }, { "affs": [ 0 ], "name": "Umberto Basile", "orcid": "0000-0002-8328-2570" } ], "bibtex": "https://research.draconitic.com/paper/8jx6h5xgaxr71.bib", "cited_by": 0, "doi": "10.3390/ijms27219447", "fulltext_url": null, "id": "8jx6h5xgaxr71", "issns": [ "1422-0067" ], "landing_url": "https://www.mdpi.com/1422-0067/27/21/9447", "language": null, "licence": "CC-BY-4.0", "licence_label": "CC BY 4.0", "licence_source": "article", "licence_url": "https://creativecommons.org/licenses/by/4.0/", "metadata_licence": null, "native_subjects": [ [ "openalex", "2720|Multiple Myeloma Research and Treatments" ] ], "openalex": "W7223307193", "pdf_url": null, "pmcid": null, "pmid": null, "published": "2026-10-23", "publisher": "MDPI AG", "ris": "https://research.draconitic.com/paper/8jx6h5xgaxr71.ris", "sources": [ { "first_seen": "2026-10-30T12:18:57Z", "native_id": "10.3390/ijms27219447", "source": "crossref", "url": "https://www.mdpi.com/1422-0067/27/21/9447" } ], "subjects": [ { "field": "medicine", "origin": "openalex:2720|Multiple Myeloma Research and Treatments", "subfield": "general" } ], "title": "Multiple Myeloma Measurable Residual Disease: Spotting Three Different Detection Methods", "title_text": "Multiple Myeloma Measurable Residual Disease: Spotting Three Different Detection Methods", "type": "peer-reviewed", "updated_at": "2026-10-30T12:18:57Z", "url": "https://research.draconitic.com/paper/8jx6h5xgaxr71", "venue": "International Journal of Molecular Sciences", "versions": [] }