Next-Generation Sequencing May Predict Progression in Multiple Myeloma

Submitted by onc_editor on Thu, 11/23/2017 - 16:26

Next-generation sequencing may help identify patients with smoldering multiple myeloma at high risk for disease progression, suggests a study to be presented at the upcoming American Society of Hematology Annual Meeting and Exposition (December 9-12, 2017; Atlanta, GA).

“Multiple myeloma is an incurable plasma cell malignancy that arises from the precursor states: monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM),” wrote Mark Bustoros, MD, Dana Farber Cancer Institute, and colleagues. “Some patients rapidly progress from MGUS/SMM to multiple myeloma, while others remain indolent with minimal progression over their lifetime.”

In 186 clinically-annotated samples from patients with smoldering multiple myeloma, researchers used next-generation sequencing methods—such as whole-exome sequencing, targeted deep sequencing, and ultra-low pass whole-genome sequencing—to identify genetic factors that distinguished progressors from nonprogressors.

Compared with patients at low risk of progressing to multiple myeloma, patients at high risk had a higher mutation load and increased incidence of somatic mutations in known signaling pathways. Mutations in MAPK pathway genes (KRAS, NRAS, BRAF) were detected in 21.7% of high-risk patients. Mutations in NFkB pathway were also associated with high risk of progression, according to the study. Multiple myeloma somatic copy number aberrations were twice as frequent in patients considered high-risk.

Phylogenetic studies of sequential samples revealed different patterns of clonal evolution in patients who had disease progression, researchers reported. Meanwhile, ultra-low pass whole-genome sequencing of cell-free DNA samples from 20 patients showed tumor fraction was higher in patients at high-risk of progressing.

“Together, this data suggests that specific genomic alterations are associated with high-risk smoldering multiple myeloma,” researchers wrote, “and could potentially be predictive of the risk to progression in smoldering multiple myeloma patients.”—Jolynn Tumolo