High-Risk Subset of Newly Diagnosed Multiple Myeloma Identified
Posted: Wednesday, September 19, 2018
A genome-wide analysis has identified a previously undescribed segment of newly diagnosed multiple myeloma with an extremely poor prognosis. Researchers refer to the high-risk subgroup as “double-hit” multiple myeloma, which is defined by two DNA-based genomic markers of “aggressive” clinical behavior and key clinical data. The study was published in Leukemia.
“Double-hit patients have a dire prognosis despite modern therapies and should be considered for novel therapeutic approaches,” stated Brian A. Walker, PhD, of the Myeloma Institute at the University of Arkansas, Little Rock, and colleagues.
As part of the Myeloma Genome Project, investigators integrated whole-genome and exome data from 1,273 patients with newly diagnosed multiple myeloma into a multivariate Cox model to identify genetic and clinical factors that contribute significantly to survival. Next, recursive partitioning was performed to identify those at high risk for early disease progression in 784 patients with complete data.
The double-hit subgroup comprised 6.1% of the total patient population and included patients who had either bi-allelic inactivation of TP53 or International Staging System stage III with amplification of CKS1B. This high-risk subgroup had a median progression-free survival of 15.4 months, significantly worse than the 784-patient cohort at 31.2 months. Researchers determined that the bi-allelic inactivation of TP53, present in 3.7% of patients with newly diagnosed multiple myeloma, is the “crucial driver” of prognosis (P < .0001).
“These patients can be readily identified using [next-generation sequencing]-based assays, providing an opportunity to evaluate innovative therapeutic strategies, such as chimeric antigen receptor T cells, to address their unmet medical need,” concluded Dr. Walker and colleagues.
