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International Myeloma Society/International Myeloma Working Group Consensus Recommendations on the Definition of High-Risk Multiple Myeloma

Hervé Avet‐LoiseauUnité de Genomique du Myélome, Institut National de la Santé et de la Recherche Médicale, University Cancer Center of Toulouse, Toulouse, FranceFaith E. DaviesPerlmutter Cancer Center, NYU Langone Health, New York, NYMehmet SamurDepartment of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MAJill CorreUnité de Genomique du Myélome, Institut National de la Santé et de la Recherche Médicale, University Cancer Center of Toulouse, Toulouse, FranceMattia D’AgostinoDivision of Hematology, AOU Città della Salute e della Scienza di Torino, Torino, ItalyMartin KaiserDepartment of Haematology, The Royal Marsden Hospital, London, United KingdomMarc S. RaabDepartment of Medicine V, Heidelberg Myeloma Center, University Hospital and Medical Faculty Heidelberg, Heidelberg University, Heidelberg, GermanyNiels WeinholdUniversity Hospital HeidelbergNorma C. GutiérrezCentro de Investigación del CáncerBruno PaivaCancer Center Clínica Universidad de Navarra (CCUN), Centro de Investigación Médica Aplicada (CIMA LAB Diagnostics), IDISNA, CIBERONC, Pamplona, SpainPaola NeriInstitute of Cancer ResearchKatja WeiselUniversity Medical Center Hamburg-EppendorfFrancesco MauraSylvester Comprehensive Cancer CenterBrian A. WalkerIndiana University IndianapolisMark BustorosDivision of Hematology and Medical Oncology, Joan and Sanford I. Weill Department of Medicine, Sandra & Edward Meyer Cancer Center, Weill Cornell Medicine, New York, NYA. Keith StewartDivision of Hematology-Oncology, Princess Margaret Cancer Centre, Toronto, ON, CanadaSaad Z. UsmaniMyeloma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NYJens HillengaßDepartment of Medicine—Myeloma, Roswell Park Comprehensive Cancer Center, Buffalo, NYWee Joo ChngNational University Cancer Institute, SingaporeJonathan J. KeatsIntegrated Cancer Genomics Division, Translational Genomics Research Institute, Phoenix, AZJoaquín Martínez‐LópezAdam S. SperlingDana-Farber Cancer Institute, Boston, MACyrille TouzeauFenghuang ZhanUniversity of Arkansas for Medical SciencesNoopur RajeDepartment of Hematology/Oncology, Center for Multiple Myeloma, Harvard Medical School, Massachusetts General Hospital, Boston, MAMichèle CavoUniversity of BolognaNiccolò BolliFondazione IRCCS Ca' Granda Ospedale Maggiore PoliclinicoIrene M. GhobrialDepartment of Medical Oncology, Center for Early Detection and Interception of Blood Cancers, Dana-Farber Cancer Institute, Boston, MAMadhav V. DhodapkarEmory University School of Medicine, Atlanta, GASundar JagannathIcahn School of Medicine at Mount Sinai, New York, NYAndrew SpencerMonash UniversitySamir ParekhDepartment of Medicine, Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NYNizar J. BahlisArnie Charbonneau Cancer Institute, University of Calgary, Calgary, CanadaSagar LonialWinship Cancer Institute, Emory University, Atlanta, GAPieter SonneveldDepartment of Hematology, EMN/Erasmus MC Cancer Institute, Rotterdam, the NetherlandsP. Leif BergsagelDivision of Hematology, Mayo Clinic, Phoenix, AZRobert Z. OrlowskiDepartments of Lymphoma/Myeloma and Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TXGareth J. MorganPerlmutter Cancer Center, NYU Langone Health, New York, NYMaría‐Victoria MateosCentro de Investigación Biomédica en Red de CáncerS. Vincent RajkumarDivision of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MNJesús F. San MiguelCentro de Investigación Biomédica en Red de CáncerKenneth C. AndersonDana-Farber Cancer InstitutePhilippe MoreauShaji KumarDivision of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MNFelipe PrósperHematology and Cell Therapy and Program of Hematology-Oncology CIMA, Clinica Universidad de Navarra, IdISNA, CIBERONC, Pamplona, SpainNikhil C. MunshiDepartment of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA

2025en

ABI

Annotatsiya

Despite significant improvements in survival of patients with multiple myeloma (MM), outcomes remain heterogeneous, and a significant proportion of patients experience suboptimal outcomes. Importantly, traditional prognostic factors based on data from patients treated with older therapies no longer capture prognosis accurately in the contemporary era of novel triplet or quadruplet therapies. Therefore, risk stratification requires refinement in the context of available and investigational treatment options in routine practice and clinical trials, respectively. The current identification of high-risk MM (HRMM) in routine practice is based on the Revised International Staging System, which stratifies patients using a combination of widely available serum biomarkers and chromosomal abnormalities assessed via fluorescence in situ hybridization. In recent years, a substantial body of evidence concerning additional clinical, biological, and molecular/genomic prognostic factors has accumulated, along with new MM risk stratification tools and consensus reports. The International Myeloma Society, along with the International Myeloma Working Group, convened an Expert Panel with the primary aim of revisiting the definition of HRMM and formulating a practical and data-driven consensus definition, based on new evidence from molecular/genomic assays, updated clinical data, and contemporary risk stratification concepts. The Panel proposes the following Consensus Genomic Staging (CGS) of HRMM which relies upon the presence of at least one of these abnormalities: (1) del(17p), with a cutoff of >20% clonal fraction, and/or TP53 mutation; (2) an IgH translocation including t(4;14), t(14;16), or t(14;20) along with 1q+ and/or del(1p32); (3) monoallelic del(1p32) along with 1q+ or biallelic del(1p32); or (4) β2 microglobulin ≥5.5 mg/L with normal creatinine (<1.2 mg/dL).

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DOI: 10.1200/jco-24-01893

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