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

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 <i>TP53</i> 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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Publication Details

Journal
Journal of Clinical Oncology
Published
2025-06-09
DOI
https://doi.org/10.1200/jco-24-01893
Citations
92
Primary Topic
Multiple Myeloma Research and Treatments
Type
article
Field-Weighted Citation Impact
162.84

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article

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

Andrew Spencer, Fenghuang Zhan, Pieter Sonneveld, Mark Bustoros et al.
92 citations
Journal of Clinical Oncology
Multiple Myeloma Research and Treatments
162.84
article

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

Andrew Spencer, Fenghuang Zhan, Pieter Sonneveld, Mark Bustoros, Mattia D’Agostino, P. Leif Bergsagel, Saad Z. Usmani, Felipe Prósper, A. Keith Stewart, Jesús F. San Miguel, Katja Christina Weisel, Irene M. Ghobrial, Sagar Lonial, Shaji Kunnathu Kumar, Sundar Jagannath, María‐Victoria Mateos, Jill Corre, Samir Sunil Parekh, Kenneth Carl Anderson, Joaquín Martínez‐López, Faith E. Davies, Robert Zygmunt Orlowski, Mehmet Samur, Brian A. Walker, Nikhil C. Munshi, Norma C. Gutiérrez, Niccolò Bolli, Noopur S Raje, Niels Weinhold, Bruno Paiva, Cyrille Touzeau, Hervé Avet‐Loiseau, Paola Neri, Nizar Jacques Bahlis, Wee Joo Chng, S. Vincent Rajkumar, Jens Hillengaß, Marc S. Raab, Michèle Cavo, Martin Kaiser, Adam S. Sperling, Jonathan J. Keats, Madhav V. Dhodapkar, Francesco Maura, Gareth J. Morgan, Philippe Moreau
article en
92 citations

Abstract

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 <i>TP53</i> 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).

Journal of Clinical OncologyVol. 43(24)
Indiana University Health (US), Translational Genomics Research Institute (US), Roswell Park Comprehensive Cancer Center (US), Memorial Sloan Kettering Cancer Center (US), The University of Texas MD Anderson Cancer Center (US), Harvard University (US), Institute of Cancer Research (GB), University of Miami (US), Emory University (US), Inserm (FR), Universität Hamburg (DE), National University of Singapore (SG), University of Calgary (CA), University of Milan (IT), Cornell University (US), Heidelberg University (DE), The Alfred Hospital (AU), University Hospital Heidelberg (DE), Princess Margaret Cancer Centre (CA), Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (IT), Azienda Ospedaliera Citta' della Salute e della Scienza di Torino (IT), NYU Langone Health (US), Massachusetts General Hospital (US), Institute of Cancer Research (CA), National University Cancer Institute, Singapore (SG), University Medical Center Hamburg-Eppendorf (DE), Dana-Farber Cancer Institute (US), Istituto di Ematologia di Bologna (IT), Royal Marsden Hospital (GB), Mayo Clinic in Arizona (US), Mayo Clinic Hospital (US), Winthrop Rockefeller Foundation (US), Instituto de Investigación Biomédica de Salamanca (ES), Clinica Universidad de Navarra (ES), Centro de Investigación del Cáncer (ES), Erasmus MC Cancer Institute (NL), Sylvester Comprehensive Cancer Center (US), Centro de Investigación Biomédica en Red de Cáncer (ES), Indiana University Indianapolis (US), University of Turin (IT), Indiana University – Purdue University Indianapolis (US), Monash University (AU), University of Arkansas for Medical Sciences (US), University of Bologna (IT), Icahn School of Medicine at Mount Sinai (US)
National Institutes of Health, National Cancer Institute
Partnerships for the goals
Openalex Percentile: Top 0%
Multiple Myeloma Research and Treatments
162.84
DOIOpen Access PDFOpenAlex
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