Patients with High-Risk Multiple Myeloma May Be Missed Without Gene Expression Profiling


Multiple myeloma (MM) is a rare and heterogeneous blood cancer of the plasma cells. Although therapies have been developed and combined to help fight the disease, patients with high-risk MM have limited options. In fact, patients may not even be appropriately recognized as having high-risk disease at diagnosis, according to a presentation at the all-virtual 62nd ASH Annual Meeting & Exposition.

At the conference, a team from the Netherlands, Norway, Italy, Germany, and Singapore presented work to support use of the Gene Expression Profile (GEP), the SKY92 gene signature, in testing for MM.

The researchers pooled information from six datasets on patients with MM who had data available regarding GEP, fluorescence in situ hybridization (FISH), International Staging System (ISS), and overall survival. The total sample was 805.

The team grouped the patients into three groups based on SKY92 gene signature and ISS data: 188 with low-risk disease (23%), 448 with intermediate-risk disease (56%), and 169 with high-risk disease (21%). The researchers also divided the groups according to FISH. They then compared the two methods.

For 44% of patients (n=79/179) classified as high risk according to FISH, the traditional classification proved to be correct. However, GEP identified another 90 of 169 patients (53%) with comparable poor outcomes who would have been missed. Furthermore, 30 of 179 (17%) FISH-classified high-risk patients actually had a mild course of the disease.

“Currently used risk-stratification methods are suboptimal, and the use of these markers leave 53% of high-risk patients unidentified. This might impact clinical strategy,” said presenter Pieter Sonneveld, MD, PhD, of Erasmus MC Cancer Institute, Rotterdam, the Netherlands. “GEP is an important and indispensable contributor in selecting [patients with] high-risk MM. SKY92 should be added as a risk-stratification method for a holistic view on a patient’s course of disease.”