Gains or amplification (amp) of chromosome 1q21/CKS1B are reported to be a high-risk
factor in myeloma. In this retrospective study, we analyzed the impact of CKS1B gain/amp
on overall survival in the context of other genetic aberrations, such as TP53 deletion,
FGFR3-IGH, IGH-MAF, MYEOV/CCND1-IGH, and RB1, as well as karyotype. The cohort included
132 myeloma patients with CKS1B gain/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 as CKS1B gain/amp coexisting with TP53 deletion,
or "triple hit," defined as double hit plus t(4;14)FGFR3-IGH or 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 with TP53 deletion (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 with CKS1B gain/amp is attributable
to the high number of high-risk patients in this group. The prognostic impact of CKS1B
gain/amp depends on the background karyotype and TP53 status.