NGS Panel Validates IMS/IMWG Consensus Genomic Risk Classification in 6,528 Myeloma Patients
This large validation study applied next-generation sequencing panels to 6,528 newly diagnosed multiple myeloma patients, confirming the International Myeloma Society/IMWG high-risk genomic model. The 22.4% of patients classified as high-risk had significantly shorter progression-free survival (30 vs 51 months). Conventional FISH-based R-ISS criteria failed to differentiate risk within the genomic subgroups, demonstrating that NGS-based genomic staging provides superior prognostic stratification and should become the standard for myeloma risk assessment.
The original study
High-risk genomic consensus validation for patients with newly diagnosed multiple myeloma using next-generation sequencing.
- Authors
- Schavgoulidze A, Perrot A, Leleu X, Cazaubiel T, Chretien ML, Feugier P, et al.
- Journal
- Blood
- Type
- Journal Article, Validation Study
- PMID
- 40991836
Original 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.