Novel Approach to Risk Stratification in Patients With Myeloma Harboring Translocations

By: Vanessa A. Carter, BS
Posted: Tuesday, May 30, 2023

Mehmet Samur, PhD, of Dana-Farber Cancer Institute, Boston, and colleagues generated and compared large whole-genome sequencing and transcriptome data from patients with multiple myeloma who do and do not harbor translocation events between chromosome 4 (NSD2 gene) and chromosome 14 (t[4;14]). Published in the journal Blood, these data demonstrate the potential to aid in the development of a DNA sequencing–based assay to molecularly identify these translocations, refine risk stratification criteria, and develop therapies for this patient population.

“Our results could have practical application for the diagnosis of high-risk patients by using either a next-generation sequencing– or polymerase chain reaction–based approach to identify high-risk t(4;14) patients in lieu of the current fluorescence in situ hybridization [FISH]-based methods,” the investigators concluded. “These data, along with previous publications identifying high-risk del17p and amp1q as high-risk features in multiple myeloma, make a scientific case to discuss modifications to the Revised International Staging System criteria,” they added.

Whole-genome and transcriptome data were generated from 258 t(4;14) and 183 non-t(4;14) chromosomes from patients with newly diagnosed multiple myeloma who had associated clinical data available. FISH analysis was performed with probes targeting t(4;14), and the percentage of involved plasma cells from bone marrow were evaluated; those with 30% positive cells were deemed positive for t(4;14).

Survival analysis revealed that approximately 25% of patients with t(4;14) had an overall survival of up to 24 months. Comparative analysis identified associated biomarkers located in the NSD2 gene and the expression of immunoglobulin heavy chain-NSD2 fusion transcripts. Of note, there appeared to be a significant difference in median overall survival based on the location of DNA breakpoints: 28.6 months for late disruption (within NSD2); 59.2 months for early disruption (in the 5' untranslated region); and 75.1 months for no disruption (upstream of NSD2).

Disclosure: For full disclosures of the study authors, visit ashpublications.org.

Blood

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