Hyperdiploid multiple myeloma: A heterogeneous entity requiring refined risk stratification—Insights from chromosome count and cytogenetic abnormalities

Summary Hyperdiploidy (HRD) is the most common genetic subtype in multiple myeloma (MM) but with significant prognostic heterogeneity. In this integrated Single Nucleotide Polymorphism (SNP‐array) and Fluorescence In Situ Hybridization (FISH) analysis of 694 newly diagnosed Chinese MM patients, a modal chromosome count >49 predicted superior overall survival (OS, p = 0.0062) and progression‐free survival (PFS, p = 0.00037), outperforming other metrics. Gain of chromosome 3 was favourable for OS ( p = 0.0024) and PFS ( p = 0.00078). Notably, HRD improved OS in patients with isolated 1q21 + ( p = 0.011) but not in those harbouring high‐risk abnormalities (t(4;14), t(14;16), 17p − or 1p32 − ). The prognostic value of modal count was cytogenetic abnormality (CA)‐dependent: in HRD without high‐risk CAs, >49 conferred better OS ( p = 0.01) and PFS ( p = 0.001); in isolated 1q21 + , a favourable trend was observed; but no discrimination in other high‐risk CAs. Autologous haematopoietic stem cell transplantation (AHSCT) significantly improved OS ( p = 0.014) and showed a PFS trend ( p = 0.062) only in HRD patients without high‐risk CAs and with >49 chromosomes. In conclusion, modal chromosome count >49 and chromosome 3 gain are robust favourable markers in HRD. HRD provides survival benefit in isolated 1q21 + . FISH‐based detection of trisomy 3 may offer a rapid, economical alternative for risk assessment of HRD. AHSCT benefit is restricted to low‐risk HRD with higher ploidy.