Genetic Test May Identify Patients at Risk for Disease Progression with Multiple Myeloma

A genetic test that can be administered early during treatment may help oncologists identify patients with multiple myeloma who are at an “ultra-high risk” of having their cancer progress, according to data published in Leukemia. Identifying patients with multiple myeloma who have high-risk genetics may help oncologists find alternative treatment options before the disease progresses.

“Testing for high-risk genetic features could help target myeloma treatment, focusing on the specific needs of each patient,” Dr. Martin Kaiser, of The Institute of Cancer Research in London, United Kingdom, said in a press release. “Not all patients with myeloma are the same, and we know that by better understanding their cancer’s genetic and molecular features, we can tailor their treatment much more effectively.”

To examine the combined predictive value of high-risk chromosomal abnormalities and SKY92 — a pattern of gene activity involving 92 genes linked to high-risk status — risk gene expression profiles, the researchers analyzed 329 newly diagnosed patients with multiple myeloma from the NCRI Myeloma XI trial who had previously received intensive therapy.

There have been various gene expression profiles, according to the researchers, that have been associated with outcomes in patients. However, only two have been developed into validated tests.

One of those tests, SKY92 MMprofiler, showed that 24.6% of the patients had a SKY92 high-risk tumor signature. Patients with the high-risk gene expression profile had significantly shorter progression-free survival and overall survival regardless of initial therapy and posttransplant induction.

Additionally, patients who presented with SKY92 high-risk disease appeared to not achieve a significant benefit from Revlimid (lenalidomide) monotherapy.

One hundred and sixty-one patient tumors carried no chromosomal high-risk marker, of which 12% were identified as SKY92 high-risk. A SKY92 high-risk gene expression profile in isolation was associated with shorter progression-free survival.

The researchers did note that patients with a single chromosomal high-risk marker, or no risk marker, achieved an extended progression-free survival receiving Revlimid compared with the other patients.

A percentage (9.7%) of the patients had both SKY92 high-risk status and double-hit genetic features, meaning they have two or more high-risk genetic features.

All those patients had their disease progress within four years from initial randomization and predicted overall survival at four years was 12.5%.

“Our study shows that people whose tumors have an ‘ultra-high risk’ combination of genetic features have particularly aggressive disease which doesn't respond sufficiently to standard treatment to keep their cancer at bay,” Kaiser said in the release. “The next step is to combine our results for this study with the ongoing OPTIMUM trial, which will provide us with more information on how to tailor treatment for patients at ultra-high risk based on genetic information.”