High-risk genomic consensus validation for patients with newly diagnosed multiple myeloma using next-generation sequencing
Year: 2025
Type: article
Study design: Observational Study
Abstract: 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.
Source: Blood
Authors: Anaïs Schavgoulidze, Aurore Perrot, Xavier Leleu, Titouan Cazaubiel, Marie-Lorraine Chretien, Pierre Feugier, Karim Belhadj, Salomon Manier, Murielle Roussel, Sabine Brechignac, Frédérique Orsini-Piocelle, Mohamad Mohty, Jean-Marc Schiano de Collela, Margaret Macro, Didier Adiko, Mamoun Dib, Jean Fontan, Carine Luttiau-Motard, Didier Bouscary, Laurent Pascal, Virginie Roland, François Lifermann, Jana Bakala, Lydia Montes, Céline 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
Institutions: Centre Hospitalier Universitaire de Toulouse, Centre de Recherches en Cancérologie de Toulouse, Institut universitaire du cancer de Toulouse Oncopole, Université de Toulouse, Centre Hospitalier Universitaire de Poitiers, Centre Hospitalier Universitaire de Bordeaux, Institut de Cancérologie de Bourgogne, CHU Dijon Bourgogne, Inserm, Centre Hospitalier Régional et Universitaire de Nancy, Nutrition-Génétique et Exposition aux Risques Environnementaux, Centre Hospitalier Universitaire Henri-Mondor, Assistance Publique – Hôpitaux de Paris, Hôpitaux Universitaires Henri-Mondor, Centre Hospitalier Universitaire de Lille, Centre Hospitalier Universitaire de Limoges, Hôpital Universitaire Dupuytren, Hôpital Avicenne, Centre Hospitalier Annecy Genevois, Sorbonne Université, Hôpital Saint-Antoine, Centre de Recherche Saint-Antoine, Institut Paoli-Calmettes, Centre Hospitalier Universitaire de Caen Normandie, Centre Hospitalier Universitaire d'Angers, Centre Hospitalier Universitaire de Besançon, Centre Hospitalier de Niort, Hôpital Cochin, Groupe Hospitalier de l'Institut Catholique de Lille, Centre Hospitalier de Perpignan, Centre Hospitalier de Dax –Côte d’Argent, Centre Hospitalier de Lens, Centre Hospitalier Universitaire Amiens-Picardie, Centre Hospitalier William Morey, Centre Léon Bérard, Centre Hospitalier Universitaire de Nice, Hôpital l'Archet, Centre Hospitalier de Valenciennes, Hôpital Necker-Enfants Malades, Centre National de la Recherche Scientifique, Institut des Maladies Génétiques Imagine, Laboratoire d'hématologie, Centre Hospitalier Universitaire de Clermont-Ferrand, Centre Hospitalier de Roubaix, Centre Hospitalier Universitaire de Saint-Étienne, Institut Bergonié, Centre Hospitalier de La Rochelle
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W4414459717