Multiple Myeloma Measurable Residual Disease: Spotting Three Different Detection Methods
9 affiliations
- 1Unit of Clinical Pathology, Santa Maria Goretti Hospital, 04100 Latina, Italy
- 2Unità Operativa Complessa Ematologia con Trapianto, Santa Maria Goretti Hospital, 04100 Latina, Italy
- 3Clinical 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
- 4Struttura Complessa Interaziendale Laboratorio Analisi Chimico Cliniche e Microbiologiche—Azienda Ospedaliera Santa Croce e Carle, 12100 Cuneo, Italy
- 5Dipartimento di Medicina e Chirurgia Traslazionale, Sezione di Patologia Generale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
- 6Fondazione Policlinico Universitario “A. Gemelli”—Istituto di Ricovero e Cura a Carattere Scientifico (I.R.C.C.S.), 00168 Rome, Italy
- 7Unità Operativa Complessa-Medicina Trasfusionale, Santa Maria Goretti Hospital, 04100 Latina, Italy
- 8Dipartimento di Medicina Traslazionale e Medicina di Precisione, La Sapienza Università di Roma, 00185 Rome, Italy
- 9Unità Operativa Complessa-Ematologia, Ospedale S. Maria Goretti, 04100 Latina, Italy
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.
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BibTeX
@article{tartaglione2026multiple,
title = {{Multiple Myeloma Measurable Residual Disease: Spotting Three Different Detection Methods}},
author = {Sara Tartaglione and Marzia Tagliaferro and Maria Cristina Scerpa and Valerio Basile and Francesca D’Ambrosio and Patrizia Natali and Mariapaola Marino and Francesco Equitani and Luca Maurillo and Umberto Basile},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27219447},
url = {https://www.mdpi.com/1422-0067/27/21/9447},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Multiple Myeloma Measurable Residual Disease: Spotting Three Different Detection Methods
AU - Sara Tartaglione
AU - Marzia Tagliaferro
AU - Maria Cristina Scerpa
AU - Valerio Basile
AU - Francesca D’Ambrosio
AU - Patrizia Natali
AU - Mariapaola Marino
AU - Francesco Equitani
AU - Luca Maurillo
AU - Umberto Basile
PY - 2026
DA - 2026/10/23
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27219447
UR - https://www.mdpi.com/1422-0067/27/21/9447
AB - 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.
SN - 1422-0067
ER -