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

The prognostic heterogeneity of multiple myeloma is mainly driven by the genomic features of myeloma cells. The International Myeloma Society (IMS)/International Myeloma Working Group (IMWG) recently proposed a high-risk (HR) genomic model to have a consensus definition of genomic risk. We performed next-generation sequencing in the form of a panel on samples from 6528 patients with newly diagnosed multiple myeloma (NDMM) and 1583 patients at first relapse between 2019 and 2024. We observed that 22.4% of patients at diagnosis and 36.7% of patients at first relapse were classified as high risk according to the Consensus Genomic Staging. Clinical data were available for 2695 patients at diagnosis. After a median follow-up of 35 months, the median progression-free survival (PFS) was 30 months for patients with HR NDMM and 51 months for standard-risk (SR) patients (P< .0001). The HR cytogenetic criteria from the Revised- International Staging System score were not able to differentiate between HR and SR patients based on the IMS/IMWG genomic subgroups. Looking at each criterion 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 reduced the PFS when compared with SR patients. Moreover, patients with several cumulating criteria had an even worse prognosis. Among SR patients, classified according to the genomic definition with normal creatinine, the median PFS for those with high β2-microglobulin was not significantly different from that of patients with normal β2-microglobulin level. This study validated the IMS/IMWG genomic definition of HR myeloma in a large cohort of patients diagnosed from 2019 onwards.

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Journal
Blood
Published
2025-09-24
DOI
https://doi.org/10.1182/blood.2025029999
Citations
3
Primary Topic
Multiple Myeloma Research and Treatments
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article
Field-Weighted Citation Impact
5.31
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article

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

François Lifermann, Isabelle Plantier, Anaïs Schavgoulidze, Faiza Keddar et al.
3 citations
Blood
Multiple Myeloma Research and Treatments
5.31
article

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

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

Abstract

The prognostic heterogeneity of multiple myeloma is mainly driven by the genomic features of myeloma cells. The International Myeloma Society (IMS)/International Myeloma Working Group (IMWG) recently proposed a high-risk (HR) genomic model to have a consensus definition of genomic risk. We performed next-generation sequencing in the form of a panel on samples from 6528 patients with newly diagnosed multiple myeloma (NDMM) and 1583 patients at first relapse between 2019 and 2024. We observed that 22.4% of patients at diagnosis and 36.7% of patients at first relapse were classified as high risk according to the Consensus Genomic Staging. Clinical data were available for 2695 patients at diagnosis. After a median follow-up of 35 months, the median progression-free survival (PFS) was 30 months for patients with HR NDMM and 51 months for standard-risk (SR) patients (P< .0001). The HR cytogenetic criteria from the Revised- International Staging System score were not able to differentiate between HR and SR patients based on the IMS/IMWG genomic subgroups. Looking at each criterion 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 reduced the PFS when compared with SR patients. Moreover, patients with several cumulating criteria had an even worse prognosis. Among SR patients, classified according to the genomic definition with normal creatinine, the median PFS for those with high β2-microglobulin was not significantly different from that of patients with normal β2-microglobulin level. This study validated the IMS/IMWG genomic definition of HR myeloma in a large cohort of patients diagnosed from 2019 onwards.

BloodVol. 147(3)
LeTourneau University (US), Hôpital Necker-Enfants Malades (FR), Centre National de la Recherche Scientifique (FR), Inserm (FR), Université Fédérale de Toulouse Midi-Pyrénées (FR), Centre Hospitalier Universitaire de Bordeaux (FR), Centre Hospitalier Universitaire de Lille (FR), Centre Hospitalier Universitaire de Nice (FR), Centre Hospitalier Universitaire Henri-Mondor (FR), Sorbonne Université (FR), Centre Hospitalier de Roubaix (FR), Centre Hospitalier Universitaire de Besançon (FR), Centre Hospitalier de Perpignan (FR), Université Sorbonne Paris Nord (FR), Hôpital Cochin (FR), Centre Hospitalier Universitaire Amiens-Picardie (FR), Assistance Publique – Hôpitaux de Paris (FR), Institut universitaire du cancer de Toulouse Oncopole (FR), Centre Hospitalier Régional et Universitaire de Nancy (FR), Hôpital Saint-Antoine (FR), University of Clermont Auvergne (FR), Centre Léon Bérard (FR), Centre Hospitalier de Lens (FR), Centre Hospitalier de Niort (FR), Centre Hospitalier Universitaire de Poitiers (FR), Institute Cancer De La Loire Lucien Neuwirth (FR), Institut de Cancérologie de Bourgogne (FR), Centre Hospitalier Universitaire d'Angers (FR), Centre Hospitalier Universitaire de Caen Normandie (FR), CHU Dijon Bourgogne (FR), Hôpital l'Archet (FR), Centre Hospitalier Universitaire de Limoges (FR), Centre Hospitalier Universitaire Notre Dame des Secours (LB), Centre Hospitalier Universitaire de Clermont-Ferrand (FR), Hôpital Avicenne (FR), Centre Hospitalier Annecy Genevois (FR), Institut Bergonié (FR), Centre de Recherche Saint-Antoine (FR), Groupe Hospitalier de l'Institut Catholique de Lille (FR), Centre Hospitalier de La Rochelle (FR), Maison des Sciences sociales et des Humanités de Dijon (FR), Centre Hospitalier de Dax –Côte d’Argent (FR), Centre Hospitalier Public du Cotentin (FR), Lux Research (United States) (US), Institut Paoli-Calmettes (FR), Laboratoire de Génétique Cellulaire (FR), Centre Hospitalier de Valenciennes (FR), Centre Hospitalier Universitaire de Saint-Étienne (FR)
Openalex Percentile: Top 4%
Multiple Myeloma Research and Treatments
5.31
DOISourceOpenAlex
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