ASCO 2020: Genetics Predict Smoldering Myeloma Progression

A key study shared at the recent ASCO meeting showed that certain genetic features found in myeloma patients could help assess the risk of developing active myeloma. Smoldering myeloma is ia precursor condition that doesn't always progress to active myeloma, so researchers are intent to learn who may benefit from early treatment while others can "watch and wait."  

The Dana Farber Cancer Institute researchers used next-generation sequencing to study 214 patients with smoldering myeloma. They performed whole-exome sequencing on 166 tumors, including 5 with serial samples, and deep targeted sequencing on 48 tumors.

Interstingly, most patients had already acquired most of the genetic mutations needed for myeloma progression, even at the smoldering stage. They identified three pathways that identified patients with a higher risk of progressing. 

• KRAS and NRAS mutations (changes in the mitogen-activated protein kinase pathway)
• Deletion of 17p, TP53 and ATM (changes in the DNA repair pathway)
• Translocations or copy number variations of MYC 

Their findings were validated by a second smoldering myeloma group that showed that patients with any of the three features had a higher risk of progressing to active myeloma. Additionally, they found that APOBEC mutations were higher in patients who progressed to active myeloma and these patients had more rapid progression to active myeloma.

It's essential that patients at the smoldering myeloma stage use genetic testing to identify these features to help determine if and how they should be treated.