International Myeloma Society/International Myeloma Working Group Consensus Recommendations on the Definition of High-Risk Multiple Myeloma
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 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).
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (46)
Hervé Avet-Loiseau
Unité Génomique du Myélome, Hôpital Universitaire de Toulouse Oncopole, Université de Toulouse, Toulouse, France
Faith E. Davies
1Multiple Myeloma Research Program, Perlmutter Cancer Center, NYU Langone Health, New York, NY
Mehmet K. Samur
Dana-Farber Cancer Institute and Harvard School of Public Health, Boston, Massachusetts, United States
Jill Corre
Unité Génomique du Myélome, Hôpital Universitaire de Toulouse Oncopole, Université de Toulouse, Toulouse, France
Mattia D'Agostino
5Division of Hematology, AOU Città della Salute e della Scienza di Torino, University of Torino and Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy
Martin F. Kaiser
4Division of Genetics and Epidemiology, The Institute of Cancer Research, London, United Kingdom
Marc S. Raab
Niels Weinhold
Norma C. Gutierrez
Hospital Universitario de Salamanca. IBSAL. Centro de Investigación del Cáncer, Salamanca, Spain
Bruno Paiva
Paola Neri
1University of Calgary
Katja Weisel
Francesco Maura
Memorial Sloan Kettering Cancer Center, New York
Brian A. Walker
Division of Hematology and Oncology, School of Medicine, Melvin and Bren Simon Comprehensive Cancer Center, Indiana University, Indianapolis, IN
Mark Bustoros
A. Keith Stewart
1Princess Margaret Cancer Centre, University Health Network, Toronto, Canada
Saad Z. Usmani
Memorial Sloan Kettering Cancer Center, New York
Jens Hillengass
Roswell Park Comprehensive Cancer Center
Wee Joo Chng
Jonathan J. Keats
TGen, Phoenix, AZ
Joaquín Martínez-López
Hospital Universitario 12 de Octubre, Instituto de Investigación Sanitaria Hospital 12 de Octubre, Complutense University of Madrid, Centro Nacional de Investigaciones Oncológicas, Madrid Institute of Cancer, Madrid
Adam S. Sperling
Brigham and Women’s Hospital
Cyrille Touzeau
Fenghuang Zhan
Noopur S. Raje
1Cellular Immunotherapy Program, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA
Michele Cavo
Niccolò Bolli
1Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico
Irene M. Ghobrial
Madhav V. Dhodapkar
1Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA
Sundar Jagannath
Icahn School of Medicine at Mount Sinai, New York
Andrew Spencer
Samir Parekh
Icahn School of Medicine at Mount Sinai, New York
Nizar J. Bahlis
Arnie Charbonneau Cancer Institute, University of Calgary, Calgary, AB, Canada
Sagar Lonial
Emory University, Atlanta
Pieter Sonneveld
Leif Bergsagel
Robert Z. Orlowski
The University of Texas MD Anderson Cancer Center, Houston, Texas, United States
Gareth Morgan
Maria Victoria Mateos
Hospital Universitario de Salamanca, Instituto de Investigación Biomédica de Salamanca, Instituto de Biología Molecular y Celular del Cáncer (Universidad de Salamanca–Consejo Superior de Investigaciones Científicas), Centro de Investigación Biomédica en Red de Cáncer, Salamanca, Spain
S. Vincent Rajkumar
Jesus F. San Miguel
Cancer Center Clínica Universidad de Navarra (CCUN), CIMA, CIBERONC, IDISNA, Pamplona, Spain
Kenneth C. Anderson
Philippe Moreau
Shaji Kumar
Felipe Prosper
Nikhil C. Munshi