The survival impact ofCKS1Bgains or amplification is dependent on the background karyotype andTP53deletion status in patients with myeloma

Gains or amplification (amp) of chromosome 1q21/CKS1Bare reported to be a high-risk factor in myeloma. In this retrospective study, we analyzed the impact ofCKS1Bgain/amp on overall survival in the context of other genetic aberrations, such asTP53deletion,FGFR3-IGH,IGH-MAF,MYEOV/CCND1-IGH, andRB1, as well as karyotype. The cohort included 132 myeloma patients withCKS1Bgain/amp detected by fluorescence in-situ hybridization. There were 72 men and 60 women with a median age of 65 years (range 39-88 years). A normal, simple, or complex karyotype was observed in 39.5%, 5.4%, and 55% of patients, respectively. "Double hit," defined asCKS1Bgain/amp coexisting withTP53deletion, or "triple hit," defined as double hit plus t(4;14)FGFR3-IGHor t(14;16)IGH-MAF, were identified in 25 patients (18.9%) and five patients (3.8%), respectively. Double and triple hit were highly associated with a complex karyotype (p = 0.02). Ninety-nine patients (99/128, 77.3%) received stem cell transplantation. The median follow-up time was 48.2 months (range 2-104 months); 68 patients (51.5%) died, with a median overall survival of 58.8 months. Multivariate analysis (Cox model) showed that double hit withTP53deletion (p = 0.0031), triple hit (p = 0.01), and complex karyotype (p = 0.0009) were each independently associated with poorer overall survival. Stem cell transplantation was associated with better overall survival, mainly in patients with a double or triple hit and complex karyotype (p = 0.003). These findings indicate that the inferior outcome of myeloma patients withCKS1Bgain/amp is attributable to the high number of high-risk patients in this group. The prognostic impact ofCKS1Bgain/amp depends on the background karyotype andTP53status.