Given the evolving understanding of genetic risk factors in multiple myeloma (MM), this paper assesses whether next-generation sequencing (NGS) could complement or even replace fluorescence in situ hybridization (FISH) at diagnosis. A structured consensus process within European Myeloma Network (EMN) clinical and laboratory groups was conducted to establish recommendations on routine clinical deployment of NGS in MM risk assessment. Four key questions were addressed: (1) should NGS be used in addition to, or alternatively to FISH in identifying prognostic genetic markers, (2) which prognostic markers are most relevant for analysis by NGS, (3) which patients should be offered NGS testing, and (4) what is the optimal timing for performing NGS. The panel reviewed current literature, evaluated available NGS technologies, and compared their performance with that of FISH-based methodologies. The paper reviews current standard NGS protocols, quality control measures, and provides practical points for the implementation of an NGS diagnosis in MM. While NGS shows promise in improving risk stratification, challenges such as cost, accessibility, and clinical workflow integration must be addressed. The consensus supports the initial incorporation of NGS as a complementary tool to FISH. Recommendations emphasize that: a broader list of genetic events should be incorporated into such a test than what currently requested by risk scores; the test should be offered at least to the fit patients who could be candidates for modern triplet or quadruplet treatments; the test should be repeated at the time relapse, especially in the future when targeted treatments may mandate the use of predictive markers of response. This consensus provides a foundation for future research and policy development, guiding the adoption of NGS in MM risk assessment.

Department of Biomedical Laboratory Science Norwegian University of Science and Technology Trondheim Norway

Department of Clinical Therapeutics School of Medicine National and Kapodistrian University of Athens Athens Greece

Department of Hematology Amsterdam UMC Vrije Universiteit Amsterdam Amsterdam The Netherlands

Department of Hematology Erasmus MC Cancer Institute Rotterdam The Netherlands

Department of Hematology Oncology and Bone Marrow Transplantation With Section of Pneumology University Medical Center Hamburg Eppendorf Hamburg Germany

Department of Hematology Oncology and Stem Cell Transplantation Medical Center University of Freiburg Faculty of Medicine University of Freiburg Freiburg Germany

Department of Hematology Oslo Myeloma Center Oslo University Hospital Oslo Norway

Department of Hematology University Hospital Marqués de Valdecilla University of Cantabria Santander Spain

Department of Hematology University Hospital of Salamanca IBSAL Cancer Research Center IBMCC CIBERONC Salamanca Spain

Department of Hematooncology Faculty of Medicine University of Ostrava and University Hospital Ostrava Ostrava Czech Republic

Department of Immunology and Transfusion Medicine St Olav's Hospital Trondheim Norway

Department of Internal Medicine 2 University Hospital of Würzburg Würzburg Germany

Department of Medical and Surgical Science University of Bologna Bologna Italy

Department of Medicine 5 Hematology Oncology and Rheumatology Heidelberg Myeloma Center Heidelberg University Hospital Heidelberg Germany

Department of Molecular Biotechnology and Health Sciences University of Torino Torino Italy

Department of Oncology and Hemato Oncology University of Milan Milan Italy

Department of Precision and Regenerative Medicine and Ionian Area Aldo Moro University School of Medicine Bari Italy

Division of Genetics and Epidemiology The Institute of Cancer Research London United Kingdom

Division of Hematology AOU Citta della Salute e della Scienza di Torino Torino Italy

Hemato Oncology Unit Hematology Department Fundação Champalimaud Lisbon Portugal

Hematology Department University Hospital Hotel Dieu Nantes France

Hematology Section Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milan Italy

HOCH Cantonal Hospital St Gallen Division Oncology Hematology St Gallen Switzerland

IRCCS Azienda Ospedaliero Universitaria di Bologna Istituto di Ematologia Seràgnoli Bologna Italy

Unit of Hematology and Stem Cell Transplantation AOUC Policlinico Bari Italy

Zobrazit více v PubMed

Morgan GJ, Walker BA, Davies FE. The genetic architecture of multiple myeloma. Nat Rev Cancer. 2012;12(5):335‐348. PubMed

Da Vià MC, Ziccheddu B, Maeda A, Bagnoli F, Perrone G, Bolli N. A journey through myeloma evolution: from the normal plasma cell to disease complexity. HemaSphere. 2020;4(6):e502. PubMed PMC

Fonseca R, Debes‐Marun CS, Picken EB, et al. The recurrent IgH translocations are highly associated with nonhyperdiploid variant multiple myeloma. Blood. 2003;102(7):2562‐2567. PubMed

Bianchi G, Munshi NC. Pathogenesis beyond the cancer clone(s) in multiple myeloma. Blood. 2015;125(20):3049‐3058. PubMed PMC

Rajkumar SV, Dimopoulos MA, Palumbo A, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol. 2014;15(12):e538‐e548. PubMed

Granell M, Calvo X, Garcia‐Guiñón A, et al. Prognostic impact of circulating plasma cells in patients with multiple myeloma: implications for plasma cell leukemia definition. Haematologica. 2017;102(6):1099‐1104. PubMed PMC

Rustad EH, Yellapantula V, Leongamornlert D, et al. Timing the initiation of multiple myeloma. Nat Commun. 2020;11(1):1917. PubMed PMC

Maura F, Kaddoura M, Poos AM, et al. Temporal genomic dynamics shape clinical trajectory in multiple myeloma. Nat Genet. 2025;57(9):2203‐2214. 10.1038/s41588-025-02292-1 PubMed DOI

Samur MK, Aktas Samur A, Shah P, et al. Development of hyperdiploidy starts at an early age and takes a decade to complete. Blood. 2025;145(5):520‐525. PubMed

Maura F, Bolli N, Angelopoulos N, et al. Genomic landscape and chronological reconstruction of driver events in multiple myeloma. Nat Commun. 2019;10(1):3835. PubMed PMC

Walker BA, Wardell CP, Melchor L, et al. Intraclonal heterogeneity is a critical early event in the development of myeloma and precedes the development of clinical symptoms. Leukemia. 2014;28(2):384‐390. PubMed PMC

Rustad EH, Yellapantula VD, Glodzik D, et al. Revealing the impact of structural variants in multiple myeloma. Blood Cancer Discov. 2020;1(3):258‐273. PubMed PMC

Chapman MA, Lawrence MS, Keats JJ, et al. Initial genome sequencing and analysis of multiple myeloma. Nature. 2011;471(7339):467‐472. PubMed PMC

Bolli N, Avet‐Loiseau H, Wedge DC, et al. Heterogeneity of genomic evolution and mutational profiles in multiple myeloma. Nat Commun. 2014;5:2997. PubMed PMC

Lohr JG, Stojanov P, Carter SL, et al. Widespread genetic heterogeneity in multiple myeloma: implications for targeted therapy. Cancer Cell. 2014;25(1):91‐101. PubMed PMC

Walker BA, Mavrommatis K, Wardell CP, et al. Identification of novel mutational drivers reveals oncogene dependencies in multiple myeloma. Blood. 2018;132(6):587‐597. PubMed PMC

Bolli N, Biancon G, Moarii M, et al. Analysis of the genomic landscape of multiple myeloma highlights novel prognostic markers and disease subgroups. Leukemia. 2018;32(12):2604‐2616. PubMed PMC

Maura F, Rajanna AR, Ziccheddu B, et al. Genomic classification and individualized prognosis in multiple myeloma. J Clin Oncol. 2024;42(11):1229‐1240. PubMed PMC

Terragna C, Poletti A, Solli V, et al. Multi‐dimensional scaling techniques unveiled gain1q&loss13q co‐occurrence in multiple myeloma patients with specific genomic, transcriptional and adverse clinical features. Nat Commun. 2024;15(1):1551. PubMed PMC

Skerget S, Penaherrera D, Chari A, et al. Comprehensive molecular profiling of multiple myeloma identifies refined copy number and expression subtypes. Nat Genet. 2024;56(9):1878‐1889. PubMed PMC

Greipp PR, Miguel JS, Durie BGM, et al. International Staging System for multiple myeloma. J Clin Oncol. 2005;23(15):3412‐3420. PubMed

Palumbo A, Avet‐Loiseau H, Oliva S, et al. Revised International Staging System for multiple myeloma: a report from International Myeloma Working Group. J Clin Oncol. 2015;33(26):2863‐2869. PubMed PMC

D'Agostino M, Zaccaria GM, Ziccheddu B, et al. Early relapse risk in patients with newly diagnosed multiple myeloma characterized by next‐generation sequencing. Clin Cancer Res. 2020;26(18):4832‐4841. PubMed

Weinhold N, Salwender HJ, Cairns DA, et al. Chromosome 1q21 abnormalities refine outcome prediction in patients with multiple myeloma—a meta‐analysis of 2,596 trial patients. Haematologica. 2021;106(10):2754‐2758. PubMed PMC

D'Agostino M, Cairns DA, Lahuerta JJ, et al. Second Revision of the International Staging System (R2‐ISS) for overall survival in multiple myeloma: a European Myeloma Network (EMN) report within the HARMONY project. J Clin Oncol. 2022;40(29):3406‐3418. PubMed

Chng WJ, Dispenzieri A, Chim C‐S, et al. IMWG consensus on risk stratification in multiple myeloma. Leukemia. 2014;28(2):269‐277. PubMed

Rajkumar SV. Multiple myeloma: 2024 update on diagnosis, risk‐stratification, and management. Am J Hematol. 2024;99(9):1802‐1824. PubMed PMC

Perrot A, Lauwers‐Cances V, Tournay E, et al. Development and validation of a cytogenetic prognostic index predicting survival in multiple myeloma. J Clin Oncol. 2019;37(19):1657‐1665. PubMed PMC

Kumar S, Kaufman JL, Gasparetto C, et al. Efficacy of venetoclax as targeted therapy for relapsed/refractory t(11;14) multiple myeloma. Blood. 2017;130(22):2401‐2409. PubMed

Walker BA, Mavrommatis K, Wardell CP, et al. A high‐risk, double‐hit, group of newly diagnosed myeloma identified by genomic analysis. Leukemia. 2019;33(1):159‐170. PubMed PMC

Flynt E, Bisht K, Sridharan V, Ortiz M, Towfic F, Thakurta A. Prognosis, biology, and targeting of TP53 dysregulation in multiple myeloma. Cells. 2020;9(2):287. PubMed PMC

Avet‐Loiseau H, Davies FE, Samur MK, et al. International Myeloma Society/International Myeloma Working Group consensus recommendations on the definition of high‐risk multiple myeloma. J Clin Oncol. 2025;43(24):2739‐2751. PubMed

Weinhold N, Ashby C, Rasche L, et al. Clonal selection and double‐hit events involving tumor suppressor genes underlie relapse in myeloma. Blood. 2016;128(13):1735‐1744. PubMed PMC

Ziccheddu B, Biancon G, Bagnoli F, et al. Integrative analysis of the genomic and transcriptomic landscape of double‐refractory multiple myeloma. Blood Adv. 2020;4(5):830‐844. PubMed PMC

Lee H, Ahn S, Maity R, et al. Mechanisms of antigen escape from BCMA‐ or GPRC5D‐targeted immunotherapies in multiple myeloma. Nat Med. 2023;29(9):2295‐2306. PubMed PMC

Costa LJ, Banerjee R, Mian H, et al. International Myeloma Working Group immunotherapy committee recommendation on sequencing immunotherapy for treatment of multiple myeloma. Leukemia. 2025;39(3):543‐554. PubMed PMC

Bolli N, Genuardi E, Ziccheddu B, Martello M, Oliva S, Terragna C. Next‐generation sequencing for clinical management of multiple myeloma: ready for prime time? Front Oncol. 2020;10:189. doi:10.3389/fonc.2020.00189. PubMed DOI PMC

Corre J, Munshi N, Avet‐Loiseau H. Genetics of multiple myeloma: another heterogeneity level? Blood. 2015;125(12):1870‐1876. PubMed PMC

Kortuem KM, Braggio E, Bruins L, et al. Panel sequencing for clinically oriented variant screening and copy number detection in 142 untreated multiple myeloma patients. Blood Cancer J. 2016;6(2):e397. PubMed PMC

Bolli N, Li Y, Sathiaseelan V, et al. A DNA target‐enrichment approach to detect mutations, copy number changes and immunoglobulin translocations in multiple myeloma. Blood Cancer J. 2016;6(9):e467. PubMed PMC

Jiménez C, Jara‐Acevedo M, Corchete LA, et al. A next‐generation sequencing strategy for evaluating the most common genetic abnormalities in multiple myeloma. J Mol Diagn. 2017;19(1):99‐106. PubMed

Yellapantula V, Hultcrantz M, Rustad EH, et al. Comprehensive detection of recurring genomic abnormalities: a targeted sequencing approach for multiple myeloma. Blood Cancer J. 2019;9(12):101‐109. PubMed PMC

Cutler SD, Knopf P, Campbell CJV, et al. DMG26. J Mol Diagn. 2021;23(12):1699‐1714. PubMed

Sudha P, Ahsan A, Ashby C, et al. Myeloma Genome Project Panel is a comprehensive targeted genomics panel for molecular profiling of patients with multiple myeloma. Clin Cancer Res. 2022;28(13):2854‐2864. PubMed PMC

Manzoni M, Marchica V, Storti P, et al. Application of next‐generation sequencing for the genomic characterization of patients with smoldering myeloma. Cancers. 2020;12(5):1332. PubMed PMC

Poletti A, Taurisano B, Mazzocchetti G, et al. Unique molecular assay (UMA): a next‐generation sequencing targeted panel for efficient and comprehensive genomic profiling and risk stratification of multiple myeloma. Haematologica. Published online May 15, 2025. 10.3324/haematol.2025.287559 PubMed DOI PMC

Höllein A, Twardziok SO, Walter W, et al. The combination of WGS and RNA‐seq is superior to conventional diagnostic tests in multiple myeloma: ready for prime time? Cancer Genet. 2020;242:15‐24. PubMed

Zhan F, Huang Y, Colla S, et al. The molecular classification of multiple myeloma. Blood. 2006;108(6):2020‐2028. PubMed PMC

Andrulis M, Lehners N, Capper D, et al. Targeting the BRAF V600E mutation in multiple myeloma. Cancer Discov. 2013;3(8):862‐869. PubMed

Cani L, Petrucci MT, Mancuso K, et al. Clinicians' perspectives and methodological application of fluorescence in situ hybridization (FISH) to define cytogenetic risk in multiple myeloma: an Italian, real‐world, survey‐based report from the European Myeloma Network (EMN) Italy. Clin Lymphoma Myeloma Leuk. 2025;25(9):676‐683. PubMed

Derrien J, Gastineau S, Frigout A, et al. Acquired resistance to a GPRC5D‐directed T‐cell engager in multiple myeloma is mediated by genetic or epigenetic target inactivation. Nat Cancer. 2023;4(11):1536‐1543. PubMed

Truger MS, Duell J, Zhou X, et al. Single‐ and double‐hit events in genes encoding immune targets before and after T cell–engaging antibody therapy in MM. Blood Adv. 2021;5(19):3794‐3798. PubMed PMC

Van De Haar J, Roepman P, Andre F, et al. ESMO recommendations on clinical reporting of genomic test results for solid cancers. Ann Oncol. 2024;35(11):954‐967. PubMed

Oben B, Froyen G, Maclachlan KH, et al. Whole‐genome sequencing reveals progressive versus stable myeloma precursor conditions as two distinct entities. Nat Commun. 2021;12(1):1861. PubMed PMC

Dutta AK, Alberge J‐B, Lightbody ED, et al. MinimuMM‐seq: genome sequencing of circulating tumor cells for minimally invasive molecular characterization of multiple myeloma pathology. Cancer Discov. 2023;13:348‐363. PubMed

Sharma N, Smadbeck JB, Abdallah N, et al. The prognostic role of PubMed PMC

Barwick BG, Neri P, Bahlis NJ, et al. Multiple myeloma immunoglobulin lambda translocations portend poor prognosis. Nat Commun. 2019;10(1):1911. PubMed PMC

Maura F, Petljak M, Lionetti M, et al. Biological and prognostic impact of APOBEC‐induced mutations in the spectrum of plasma cell dyscrasias and multiple myeloma cell lines. Leukemia. 2018;32(4):1043‐1047. PubMed PMC

Maura F, Degasperi A, Nadeu F, et al. A practical guide for mutational signature analysis in hematological malignancies. Nat Commun. 2019;10(1):2969. PubMed PMC

Diamond BT, Baughn LB, Poorebrahim M, et al. Biallelic antigen escape is a mechanism of resistance to anti‐CD38 antibodies in multiple myeloma. Blood. Published online June 10, 2025. 10.1182/blood.2024028107 PubMed DOI PMC

Lohr JG, Kim S, Gould J, et al. Genetic interrogation of circulating multiple myeloma cells at single‐cell resolution. Sci Transl Med. 2016;8(363):363ra147. PubMed PMC

Dutta AK, Fink JL, Grady JP, et al. Subclonal evolution in disease progression from MGUS/SMM to multiple myeloma is characterised by clonal stability. Leukemia. 2019;33(2):457‐468. PubMed PMC

Manier S, Park J, Capelletti M, et al. Whole‐exome sequencing of cell‐free DNA and circulating tumor cells in multiple myeloma. Nat Commun. 2018;9(1):1691. PubMed PMC

Manzoni M, Pompa A, Fabris S, et al. Limits and applications of genomic analysis of circulating tumor DNA as a liquid biopsy in asymptomatic forms of multiple myeloma. HemaSphere. 2020;4(4):e402. PubMed PMC

Waldschmidt JM, Yee AJ, Vijaykumar T, et al. Cell‐free DNA for the detection of emerging treatment failure in relapsed/refractory multiple myeloma. Leukemia. 2022;36(4):1078‐1087. PubMed PMC

Martello M, Solli V, Mazzocchetti G, et al. High level of circulating cell‐free tumor DNA at diagnosis correlates with disease spreading and defines multiple myeloma patients with poor prognosis. Blood Cancer J. 2024;14(1):208. PubMed PMC

Cheng AP, Widman AJ, Arora A, et al. Error‐corrected flow‐based sequencing at whole‐genome scale and its application to circulating cell‐free DNA profiling. Nat Methods. 2025;22:973‐981. PubMed PMC

Benjamin D, Sato T, Cibulskis K, Getz G, Stewart C, Lichtenstein L. Calling somatic SNVs and indels with Mutect2. Bioninformatics. Published online December 2, 2019. 10.1101/861054 DOI

Kim S, Scheffler K, Halpern AL, et al. Strelka2: fast and accurate calling of germline and somatic variants. Nat Methods. 2018;15(8):591‐594. PubMed

Koboldt DC, Zhang Q, Larson DE, et al. VarScan 2: somatic mutation and copy number alteration discovery in cancer by exome sequencing. Genome Res. 2012;22(3):568‐576. PubMed PMC

Garrison E, Marth G, Haplotype‐based variant detection from short‐read sequencing. arXiv:1207.3907v2. doi:10.48550/arXiv.1207.3907 DOI

Talevich E, Shain AH, Botton T, Bastian BC. CNVkit: genome‐wide copy number detection and visualization from targeted DNA sequencing. PLoS Comput Biol. 2016;12(4):e1004873. PubMed PMC

Kuilman T, Velds A, Kemper K, et al. CopywriteR: DNA copy number detection from off‐target sequence data. Genome Biol. 2015;16(1):49. PubMed PMC

Chen X, Schulz‐Trieglaff O, Shaw R, et al. Manta: rapid detection of structural variants and indels for germline and cancer sequencing applications. Bioinformatics. 2016;32(8):1220‐1222. PubMed

Rausch T, Zichner T, Schlattl A, Stütz AM, Benes V, Korbel JO. DELLY: structural variant discovery by integrated paired‐end and split‐read analysis. Bioinformatics. 2012;28(18):i333‐i339. PubMed PMC

Bergsagel PL, Kuehl WM. Molecular pathogenesis and a consequent classification of multiple myeloma. J Clin Oncol. 2005;23(26):6333‐6338. PubMed

Shaughnessy JD, Zhan F, Burington BE, et al. A validated gene expression model of high‐risk multiple myeloma is defined by deregulated expression of genes mapping to chromosome 1. Blood. 2007;109(6):2276‐2284. PubMed

Decaux O, Lodé L, Magrangeas F, et al. Prediction of survival in multiple myeloma based on gene expression profiles reveals cell cycle and chromosomal instability signatures in high‐risk patients and hyperdiploid signatures in low‐risk patients: a study of the Intergroupe Francophone du Myélome. J Clin Oncol. 2008;26(29):4798‐4805. PubMed

Kuiper R, Broyl A, De Knegt Y, et al. A gene expression signature for high‐risk multiple myeloma. Leukemia. 2012;26(11):2406‐2413. PubMed

Paik S, Shak S, Tang G, et al. A multigene assay to predict recurrence of tamoxifen‐treated, node‐negative breast cancer. N Engl J Med. 2004;351(27):2817‐2826. PubMed

Roberts KG, Li Y, Payne‐Turner D, et al. Targetable kinase‐activating lesions in Ph‐like acute lymphoblastic leukemia. N Engl J Med. 2014;371(11):1005‐1015. PubMed PMC

Kaiser MF, Hall A, Walker K, et al. Daratumumab, cyclophosphamide, bortezomib, lenalidomide, and dexamethasone as induction and extended consolidation improves outcome in ultra‐high‐risk multiple myeloma. J Clin Oncol. 2023;41(23):3945‐3955. PubMed

Kaiser MF, Walker BA, Hockley SL, et al. A TC classification‐based predictor for multiple myeloma using multiplexed real‐time quantitative PCR. Leukemia. 2013;27(8):1754‐1757. PubMed

Neri P, Maity R, Alberge J‐B, et al. Mutations and copy number gains of the BCL2 family members mediate resistance to venetoclax in multiple myeloma (MM) patients. Blood. 2019;134(suppl_1):572.

Gupta VA, Barwick BG, Matulis SM, et al. Venetoclax sensitivity in multiple myeloma is associated with B‐cell gene expression. Blood. 2021;137(26):3604‐3615. PubMed PMC

Friedrich MJ, Neri P, Kehl N, et al. The pre‐existing T cell landscape determines the response to bispecific T cell engagers in multiple myeloma patients. Cancer Cell. 2023;41(4):711‐725.e6. PubMed

Bolli N, Maura F, Minvielle S, et al. Genomic patterns of progression in smoldering multiple myeloma. Nat Commun. 2018;9(1):3363. PubMed PMC

Boyle EM, Davies FE, Deshpande S, et al. Analysis of the sub‐clonal structure of smoldering myeloma over time provides a new means of disease monitoring and highlights evolutionary trajectories leading to myeloma. Blood. 2019;134(suppl_1):4333.

Bustoros M, Sklavenitis‐Pistofidis R, Park J, et al. Genomic profiling of smoldering multiple myeloma identifies patients at a high risk of disease progression. J Clin Oncol. 2020;38(21):2380‐2389. PubMed PMC

Bustoros M, Anand S, Sklavenitis‐Pistofidis R, et al. Genetic subtypes of smoldering multiple myeloma are associated with distinct pathogenic phenotypes and clinical outcomes. Nat Commun. 2022;13(1):3449. PubMed PMC

Lakshman A, Rajkumar SV, Buadi FK, et al. Risk stratification of smoldering multiple myeloma incorporating revised IMWG diagnostic criteria. Blood Cancer J. 2018;8(6):59. PubMed PMC

Mateos M‐V, Kumar S, Dimopoulos MA, et al. International Myeloma Working Group risk stratification model for smoldering multiple myeloma (SMM). Blood Cancer J. 2020;10(10):102. PubMed PMC

Hill E, Dew A, Morrison C, et al. Assessment of Discordance Among Smoldering Multiple Myeloma Risk Models. JAMA Oncol. 2020;7(1):132‐134. PubMed PMC

Mateos M‐V, Hernández M‐T, Giraldo P, et al. Lenalidomide plus dexamethasone versus observation in patients with high‐risk smouldering multiple myeloma (QuiRedex): long‐term follow‐up of a randomised, controlled, phase 3 trial. Lancet Oncol. 2016;17(8):1127‐1136. PubMed

Lonial S, Jacobus S, Fonseca R, et al. Randomized trial of lenalidomide versus observation in smoldering multiple myeloma. J Clin Oncol. 2020;38(11):1126‐1137. PubMed PMC

Musto P, Engelhardt M, Caers J, et al. 2021 European Myeloma Network review and consensus statement on smoldering multiple myeloma: how to distinguish (and manage) Dr. Jekyll and Mr. Hyde. Haematologica. 2021;106(11):2799‐2812. PubMed PMC

Dimopoulos MA, Voorhees PM, Schjesvold F, et al. Daratumumab or active monitoring for high‐risk smoldering multiple myeloma. N Engl J Med. 2025;392(18):1777‐1788. PubMed

Landgren O, Chari A, Cohen YC, et al. Efficacy and safety of daratumumab in intermediate/high‐risk smoldering multiple myeloma: final analysis of CENTAURUS. Blood. 2025;145(15):1658‐1669. PubMed

Maura F, Bolli N, Rustad EH, Hultcrantz M, Munshi N, Landgren O. Moving from cancer burden to cancer genomics for smoldering myeloma: a review. JAMA Oncol. 2020;6(3):425. PubMed PMC

Da Viá MC, Lazzaroni F, Matera A, et al. Aberrant single‐cell phenotype and clinical implications of genotypically defined polyclonal plasma cells in myeloma. Blood. 2025;145(26):3124‐3138. PubMed

Alberge J‐B, Dutta AK, Poletti A, et al. Genomic landscape of multiple myeloma and its precursor conditions. Nat Genet. 2025;57:1493‐1503. PubMed PMC

Mosca L, Musto P, Todoerti K, et al. Genome‐wide analysis of primary plasma cell leukemia identifies recurrent imbalances associated with changes in transcriptional profiles. Am J Hematol. 2013;88(1):16‐23. PubMed

Rossi A, Voigtlaender M, Janjetovic S, et al. Mutational landscape reflects the biological continuum of plasma cell dyscrasias. Blood Cancer J. 2017;7(2):e537x. PubMed PMC

Leypoldt LB, Tichy D, Besemer B, et al. Isatuximab, carfilzomib, lenalidomide, and dexamethasone for the treatment of high‐risk newly diagnosed multiple myeloma. J Clin Oncol. 2024;42(1):26‐37. PubMed PMC

Cavo M, Gay F, Beksac M, et al. Autologous haematopoietic stem‐cell transplantation versus bortezomib–melphalan–prednisone, with or without bortezomib–lenalidomide–dexamethasone consolidation therapy, and lenalidomide maintenance for newly diagnosed multiple myeloma (EMN02/HO95): a multicentre, randomised, open‐label, phase 3 study. Lancet Haematol. 2020;7(6):456. PubMed

Hari P, Pasquini MC, Stadtmauer EA, et al. Long‐term follow‐up of BMT CTN 0702 (STaMINA) of postautologous hematopoietic cell transplantation (autoHCT) strategies in the upfront treatment of multiple myeloma (MM). J Clin Oncol. 2020;38(15_suppl):8506.

Venner CP, Duggan P, Song K, et al. Tandem autologous stem cell transplantation does not benefit high‐risk myeloma patients in the maintenance era: real‐world results from the Canadian Myeloma Research Group database. Transplant Cell Ther. 2024;30(9):889‐901. PubMed

Costa LJ, Chhabra S, Medvedova E, et al. Daratumumab, carfilzomib, lenalidomide, and dexamethasone with minimal residual disease response‐adapted therapy in newly diagnosed multiple myeloma. J Clin Oncol. 2022;40(25):2901‐2912. PubMed

Mina R, Musto P, Rota‐Scalabrini D, et al. Carfilzomib induction, consolidation, and maintenance with or without autologous stem‐cell transplantation in patients with newly diagnosed multiple myeloma: pre‐planned cytogenetic subgroup analysis of the randomised, phase 2 FORTE trial. Lancet Oncol. 2023;24(1):64‐76. PubMed