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Genetic Mutation Analysis May Improve Treatment in Multiple Myeloma

Erin Wallace
Published Online:3:47 PM, Wed August 19, 2015

Gareth Morgan, MD, PhD

Genetic testing may improve treatment for multiple myeloma by helping oncologists identify patients at risk for developing more aggressive disease, according to a recent press release published by The Institute of Cancer Research.
The study, led by researchers at the Institute of Cancer Research in London and published August 17, 2015 in the Journal of Clinical Oncology, is the first to link genetic mutations within myeloma cells to survival. Findings showed that testing for nine genetic mutations, combined with testing to determine disease stage, identified 90% of patients with very aggressive multiple myeloma who died prematurely.
New or existing drugs developed for other cancers can target over 50% of mutations identified in this study. Patients who have CCND1 mutations were more likely to have severe forms of disease than those who did not.  Thirty-eight percent of patients with the CCND1 mutations survived past 2 years, compared with 80% of patients without.
TP53 was faulty in 11% of patients and associated with a shorter survival time; 54% of patients with TP53 mutations survived over 2 years. Forty-three percent of patients had NRAS and KRAS mutations. This suggests that in myeloma, RAS mutations drive cells to become cancerous, which could potentially provide new forms of treatment.
In addition, all patients with myeloma IRF4 and EGR1 mutations survived over 2 years compared with 79% and 78% of patients without, respectively.
The researchers used genetic sequencing to analyze the genes of 463 patients enrolled in the Myeloma XI clinical trial. Fifteen significantly mutated genes were identified in a subset of patients with myeloma; the relation of long-term survival to these mutations was mapped as well.
“Our study has identified genetic features, which can identify those patients whose myeloma is likely to prove aggressive and to progress quickly,” said study leader Gareth Morgan, MD, PhD, deputy director, Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, in the press release. “We hope our study ultimately paves the way for genetic testing to pick out the minority of patients with myeloma with a poor prognosis, who might benefit from the most intensive possible treatment.”

The Institute of Cancer Research. Genetic test could improve blood cancer treatment. Accessed August 18, 2015.

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