ASH 2020 | Genomic differences in SMM progressors versus non-progressors

Nikhil Munshi, MD, Dana-Farber Cancer Institute, Boston, MA, discusses an evaluation of genomic changes in smoldering multiple myeloma (SMM). SMM, a precursor disease to multiple myeloma, has a 10% progression rate to symptomatic multiple myeloma within 5 years of diagnosis. However, this is highly dependent on the genomic background. High-throughput genomic analysis was conducted in non-progressors (≥5 years follow-up), rapid progressors and newly diagnosed myeloma patients. The results showed that global chromosome number alterations and translocations were similar across the cohorts, but the overall mutational load was lower in non-progressors at diagnosis, most notably in coding regions. NRAS and BRAF mutation rates were much lower for non-progressors compared to progressors and symptomatic myeloma, as were driver mutations commonly seen in these latter two cohorts. Reduced genomic scar scores and single-nucleotide variants, downregulated MYC target genes and low DNA repair activation were among the cytogenetic features found to define low-risk SMM. This interview took place during the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition, 2020.