High-risk genomic consensus validation for patients with newly diagnosed multiple myeloma using next-generation sequencing
2 CRCT - Centre de Recherches en Cancérologie de Toulouse
3 Service Hématologie - IUCT-Oncopole [CHU Toulouse]
4 CHU de Poitiers [La Milétrie] - Centre hospitalier universitaire de Poitiers = Poitiers University Hospital
5 CHU de Bordeaux Pellegrin [Bordeaux]
6 Service d'hématologie biologique [CHU de Dijon]
7 CHRU Nancy - Centre Hospitalier Régional Universitaire de Nancy
8 CHU Henri Mondor [Créteil]
9 CANTHER - Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277
10 CHU Limoges
11 Service d'hématologie clinique [Avicenne]
12 Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois]
13 CHU Saint-Antoine [AP-HP]
14 IPC - Institut Paoli-Calmettes
15 CHU Caen Normandie - CHU Caen Normandie – Centre Hospitalier Universitaire de Caen Normandie
16 Centre Hospitalier Libourne
17 Hôpital Haut-Lévêque [CHU Bordeaux]
18 CHU Angers - Centre Hospitalier Universitaire d'Angers
19 Hôpital Jean Minjoz [Besançon]
20 IC UM3 (UMR 8104 / U1016) - Institut Cochin
21 Hôpital Saint Vincent de Paul [Lille]
22 CH Dax - Centre Hospitalier Dax - Côte d'Argent
23 Centre Hospitalier de Lens
24 CHU Amiens-Picardie
25 Service d'Accompagnement et Soins Palliatifs [CHU Limoges]
26 Centre Léon Bérard [Lyon]
27 Imagine - U1163 - Imagine - Institut des maladies génétiques (IHU)
28 CHP - CENTRE HOSPITALIER PÉRIGUEUX
29 CHU Clermont-Ferrand
30 Hôpital Victor Provo [Roubaix]
31 SAINBIOSE - Santé Ingénierie Biologie Saint-Etienne
32 CIC-EC 1408 - Centre d'Investigation Clinique - Epidémiologie Clinique [CHU Saint-Etienne]
33 ICHUSE - Institut de Cancérologie et d'Hématologie Universitaire de Saint-Étienne [CHU Saint-Etienne]
34 Institut Bergonié [Bordeaux]
35 CH la Rochelle - Centre Hospitalier de la Rochelle - Ré Aunis- Hôpital Saint Louis
36 Hôpital Claude Huriez [Lille]
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Résumé
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.
