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Publications

Journal Article Ahead of print

PubMed: 40991836 DOI: 10.1182/blood.2025029999

High-risk genomic consensus validation for patients with newly diagnosed multiple myeloma using next-generation sequencing.

Blood

Authors: Anaïs Schavgoulidze, Aurore Perrot, Xavier Leleu, Titouan Cazaubiel, Marie-Lorraine Chretien, Pierre Feugier, Karim Belhadj, Salomon Manier, Murielle Roussel, Sabine Brechignac, Frederique Orsini Piocelle, Mohamad Mohty, Jean Marc Schiano de Colella, Margaret Macro, Didier Adiko, Mamoun Dib, Jean Fontan, Carine Motard, Didier Bouscary, Laurent Pascal, Virginie Roland, Francois Lifermann, Jana Armelle Bakala, Lydia Montes, Celine Kennel, Philippe Rey, Valentine Richez, Faiza Keddar, Laurent Frenzel, Claire Calmettes, Carine Chaleteix, Isabelle Plantier, Emilie Chalayer, Anna Schmitt, Christophe Roul, Hélène Demarquette, Chloe Cerutti, Luka Pavageau, Laure Derrier, Hervé Avet-Loiseau, Jill Corre

Affiliations

  • Institut Universitaire du Cancer de Toulouse-Oncopole, Toulouse, France.
  • Université de Toulouse, CHU Toulouse, Toulouse, France.
  • Hopital La Miletrie, Poitiers, France.
  • CHU de Bordeaux, Bordeaux, France.
  • Institut de Cancérologie de Bourgogne, PolyClinique du Parc Drevon, DIJON, France.
  • Centre Hospitalier Universitaire Nancy and INSERM 1256, Nancy, France.
  • Service d'Hematologie Clinique, Hopital Henri Mondor, Creteil, Creteil, France.
  • CHU Lille, Lille, France.
  • CHU Dupuytren, Limoges, France.
  • University Hospital Avicenne, Bobigny, France.
  • Centre Hospitalier de la region d'Annecy, METZ TESSY, France.
  • Hôpital Saint-Antoine, INSERM UMRs 938, and Université Sorbonne, Paris, France.
  • Institut Paoli Calmettes, Marseille, France.
  • CHU, CAEN, France.
  • CH Libourne, LIBOURNE, France.
  • chu angers, angers, France.
  • Hôpital Minjoz, Besançon, France.
  • CH niort.
  • APHP Cochin Hospital, Paris, France.
  • GHICL, Lille, France.
  • Hopital Saint Jean, Perpignan, France.
  • CH Dax, dax, France.
  • centre hospitalier Lens, lens, France.
  • CHU Amiens, Amiens, France.
  • CH Chalon-sur-Saône, Chalon-sur-Saône, France.
  • Centre Leon Berard, Lyon, France.
  • Hôpital de l'Archet, CHU Nice.
  • CH Valenciennes, VALENCIENNES, France.
  • Service d'Hématologie Adulte et unité d'hémostase clinique, Hôpital Necker, Institut IMAGINE - INSERM U 1163 / CNRS ERL 8254, Paris France, Paris, France.
  • CH Périgueux, Hématologie Clinique, Périgueux, France, PERIGEUX, France.
  • CLERMONT FERRAND UNIVERSITY HOSPITAL, Clermont ferrand, France.
  • CENTRE HOSPITALIER ROUBAIX, ROUBAIX, France.
  • Institut de Cancérologie du CHU de ST-ETIENNE, Saint-Priest-en-Jarez, France.
  • Institut Bergonié, BORDEAUX, France.
  • CH La Rochelle, France.
  • CH Dunkerque, Dunkerque, France.
  • Institut Universitaire du Cancer de Toulouse-Oncopole, 31100, France.
  • IUCT-Oncopole, Toulouse, France.
  • Unité de Genomique du Myélome, IUC- T Oncopole, Toulouse, France.
  • IUCT-Oncopole Toulouse, Toulouse, France.
  • Unité de Genomique du Myélome, IUC- T Oncopole, TOULOUSE, France.

Abstract

The prognostic heterogeneity of multiple myeloma is mainly driven by genomic features of myeloma cells. The International Myeloma Society (IMS) / International Myeloma Working Group (IMWG) recently proposed a high-risk (HR) genomic model in order to have a consensus definition of genomic risk. We performed NGS panel in 6528 new diagnosed myeloma patients (NDMM) and 1583 patients at first relapse, between 2019 and 2024. We observed that 22.4% of patients at diagnosis and 36.7% at first relapse were HR according to the Consensus Genomic Staging (CGS). Clinical data were available for 2695 patients at diagnosis. After a median follow-up of 35 months, the median PFS was 30 months for HR NDMM patients, vs 51 months for standard-risk (SR) (p<0.0001). HR cytogenetic criteria from the Revised-ISS score were not able to discriminate patients in HR nor SR IMS/IMWG genomic subgroups. Looking at each criteria independently, we found that the presence of del(17p), TP53 mutation, biallelic del(1p32), or the combination of intermediate risk cytogenetics (gain 1q, del(1p32), t(4;14), t(14;16), t(14;20)) significantly reduces the PFS compared with standard-risk patients. Moreover, patients cumulating several criteria had an even worse prognosis. Among SR patients according to the genomic definition with normal creatinine, median PFS of those with high beta2-microglobulin was not significantly different from patients with normal beta2-microglobulin level. This study validates the IMS/IMWG genomic definition of high-risk myeloma in a large cohort of patients diagnosed from 2019.

MeSH

High-Throughput Nucleotide Sequencing, Multiple Myeloma, Diagnosis, Cytogenetics