New Genomic Score Offers Insight into Multiple Myeloma Progression

Researchers from Dana-Farber Cancer Institute, the Broad Institute of MIT and Harvard, and Massachusetts General Hospital have introduced a novel risk assessment tool that can predict the progression of multiple myeloma, a type of blood cancer. This new score, known as the MM-like score, evaluates the severity of the disease by tracing DNA mutations.

The MM-like score aims to identify patients with precursor conditions, such as monoclonal gammopathy of undetermined significance (MGUS) or smoldering multiple myeloma (SMM), who are at a higher risk of advancing to active cancer. The research suggests that a higher MM-like score correlates with a faster progression of the disease, potentially paving the way for personalized treatment strategies.

"This study enhances our understanding of how we can tailor treatment options based on genetic risk factors," stated a co-senior author involved in the study. The findings were published in the journal Nature Genetics, illustrating a significant step toward individualized care for patients in the early stages of multiple myeloma.

Each year, approximately 32,000 individuals in the United States are diagnosed with multiple myeloma. Prior to reaching this stage, patients often experience precursor stages, which can transition into active disease in 1% to 10% of cases annually. Notably, 50% of patients with high-risk SMM may progress within two years.

According to the research team, the introduction of the MM-like score addresses a critical gap in existing risk stratification models, which typically classify patients simply as "high" or "low" risk based on tumor burden. This new score incorporates genetic factors, allowing for a more nuanced view of disease progression.

"Our data provides a straightforward genomic score that can enhance the clinical markers used to stratify the risk for our patients," mentioned a director at Dana-Farber. The MM-like score is designed to evolve over time as mutations accumulate, which reflects the progression of the disease.

In their analysis, the researchers utilized whole genome sequencing data from over 1,000 individuals with multiple myeloma and precursor conditions, including 218 patients with MGUS or SMM. This comprehensive analysis represents one of the largest collections of whole genome data pertaining to multiple myeloma and its precursor stages.

"This study significantly improves our understanding of cancer-driving mutations in multiple myeloma and the timing of these mutations across various disease stages," an expert from the Broad Institute noted. The research findings indicate that the earliest genomic alterations linked to multiple myeloma may manifest early in life, potentially during a patient's 20s or 30s, despite a typical diagnosis occurring later.

The research team has also proposed developing a test based on liquid biopsies, which could replace traditional bone marrow biopsies for DNA collection. This approach may facilitate more frequent monitoring of disease evolution and progression. Ongoing validation and refinement of the MM-like score are planned as the team continues to study a larger cohort of patients over extended periods.