High-risk genomic consensus validation for patients with newly diagnosed multiple myeloma using next-generation sequencing
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.
Article Details
Authors (41)
Anaïs Schavgoulidze
Institut Universitaire du Cancer de Toulouse-Oncopole, Toulouse, France
Aurore Perrot
Xavier Leleu
Service Hématologie, Hôpital Universitaire de Poitiers, Poitiers, France
Titouan Cazaubiel
4Department of Hematology, Centre Hospitalo-Universitaire de Bordeaux, Bordeaux, France
Marie-Lorraine Chretien
5Department of Hematology, Centre Hospitalo-Universitaire de Dijon, Dijon, France
Pierre Feugier
2Service Hématologie, Centre Hospitalier Régional Universitaire de Nancy–Hôpital Brabois, Université de Lorraine, Nancy, France
Karim Belhadj
7Department of Hematology, Créteil Hospital, Assistance Publique–Hôpitaux de Paris, Paris, France
Salomon Manier
Murielle Roussel
9Department of Hematology, Centre Hospitalo-Universitaire de Limoges, Limoges, France
Sabine Brechignac
10Department of Hematology, Bobigny Hospital, Assistance Publique–Hôpitaux de Paris, Paris, France
Frédérique Orsini-Piocelle
11Department of Hematology, Centre Hospitalier Annecy Genevois, Epagny Metz-Tessy, France
Mohamad Mohty
Jean-Marc Schiano de Collela
13Department of Hematology, Institut Paoli-Calmettes, Marseille, France
Margaret Macro
Service Hématologie, Institut Hématologie de Basse Normandie, Hôpital Universitaire de Caen, Caen, France
Didier Adiko
15Department of Hematology, Centre Hospitalier Libourne, Libourne, France
Mamoun Dib
16Department of Hematology, Centre Hospitalo-Universitaire de Angers, Angers, France
Jean Fontan
17Department of Hematology, Centre Hospitalier Besançon, Besançon, France
Carine Luttiau-Motard
18Department of Hematology, Centre Hospitalier Niort, Niort, France
Didier Bouscary
19Department of Hematology, Cochin Hospital, Assistance Publique–Hôpitaux de Paris, Paris, France
Laurent Pascal
20Department of Hematology, Centre Hospitalier Saint-Vincent, Lille, France
Virginie Roland
21Department of Hematology, Centre Hospitalier Perpignan, Perpignan, France
Francois Lifermann
Jana Bakala
23Department of Hematology, Centre Hospitalier Lens, Lens, France
Lydia Montes
24Department of Hematology, Centre Hospitalo-Universitaire de Amiens, Amiens, France
Céline Kennel
25Department of Hematology, Centre Hospitalier Chalon, Chalon-sur-Saône, France
Philippe Rey
Centre Léon Bérard, Lyon, France
Valentine Richez
27Département de Hématologie, Centre Hospitalo-Universitaire de Nice, Nice, France
Faiza Keddar
28Département de Hématologie, Centre Hospitalier Valenciennes, Valenciennes, France
Laurent Frenzel
Claire Calmettes
30Department of Hematology, Centre Hospitalier Périgueux, Périgueux, France
Carine Chaleteix
Service Hématologie, Hôpital Universitaire de Clermont-Ferrand, Clermont-Ferrand, France
Isabelle Plantier
32Department of Hematology, Centre Hospitalier Roubaix, Roubaix, France
Emilie Chalayer
33Department of Hematology, Centre Hospitalo-Universitaire de Saint-Etienne, Saint-Etienne, France
Anna Schmitt
Christophe Roul
35Department of Hematology, Centre Hospitalier La Rochelle, La Rochelle, France
Hélène Demarquette
36Department of Hematology, Centre Hospitalier Dunkerque, Dunkerque, France
Chloe Cerutti
Institut Universitaire du Cancer de Toulouse-Oncopole, 31100, France
Luka Pavageau
1Unit for Genomics in Myeloma, University Hospital, University of Toulouse, Institut Universitaire du Cancer Toulouse Oncopole, Centre de Recherches en Cancérologie de Toulouse, Toulouse, France
Laure Derrier
1Unit for Genomics in Myeloma, University Hospital, University of Toulouse, Institut Universitaire du Cancer Toulouse Oncopole, Centre de Recherches en Cancérologie de Toulouse, Toulouse, France
Hervé Avet-Loiseau
Unité Génomique du Myélome, Hôpital Universitaire de Toulouse Oncopole, Université de Toulouse, Toulouse, France
Jill Corre
Unité Génomique du Myélome, Hôpital Universitaire de Toulouse Oncopole, Université de Toulouse, Toulouse, France