Multi-Omics Approach Guides Relapsed Multiple Myeloma Treatment

Many patients with relapsed multiple myeloma are not often matched with correct treatment options in a timely or personalized manner, and most patients have a median survival rate of six years. With standard diagnosis and treatment, relapses are usually inevitable and fatal for most patients.

The use of high-throughput DNA sequencing to match genetic mutations to cancer-killing drugs, allows treatment for patients with multiple myeloma. Sequencing has revealed wide heterogeneity across patients and complex sub-clonal structures, indicating that using personalized therapeutic approach can help improve patients with myeloma.

Scientists at the Mount Sinai Hospital (New York, NY, USA) and their colleagues performed a precision medicine trial using a group of 64 relapsed multiple myeloma patients. They collected 4 to 10 mL of bone aspirate, as well as peripheral blood samples, and extracted tumor genomic DNA and RNA from BM CD138+ cells. Whole-exome sequencing (WES) and RNA sequencing libraries were submitted to Illumina HiSeq2500 for paired-end sequencing (100 base pairs). Targeted sequencing was performed using the Lymphoma Extended targeted next-generation sequencing panel from Cancer Genetics.

The team generated treatment recommendations in 63 of 64 patients. Twenty-six patients had treatment implemented, and 21 were assessable. Of these, 11 received a drug that was based on RNA findings, eight received a drug that was based on DNA, and two received a drug that was based on both RNA and DNA. Sixteen of the 21 evaluable patients had a clinical response (i.e. reduction of disease marker ≥ 25%), giving a clinical benefit rate of 76% and an overall response rate of 66%, with five patients having ongoing responses at the end of the trial. The median duration of response was 131 days.

The authors concluded that a comprehensive sequencing approach can identify viable options in patients with relapsed and/or refractory myeloma, and they represent proof of principle of how RNA sequencing can contribute beyond DNA mutation analysis to the development of a reliable drug recommendation tool. The study was published in the August 2018 issue of the journal JCO Precision Oncology.

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