Genomic Sequencing Identifies Actionable Mutations in 75% of Patients With Multiple Myeloma


A recent study found that a significant number of patients with multiple myeloma harbor potentially actionable oncogenic molecular alterations, prompting a need for novel precision medicine approaches.

The study will be presented at the 59th Annual American Society of Hematology (ASH) Meeting and Exposition (December 9-12, 2017; Atlanta, GA).

Most therapeutic approaches to multiple myeloma have focused on the plasma cell biology of the disease. But novel genomic sequencing research efforts have shown that a large number of multiple myeloma cases harbor molecular mutations, suggesting that precision medicine interventions to target such mutations might be a beneficial therapeutic approach.

Daniel Auclair, PhD, Multiple Myeloma Research Foundation (Norwalk, CT), and colleagues conducted a study to evaluate the potential and clinical utility of precision medicine approaches in multiple myeloma on a larger scale. The MMRF Molecular Profiling Protocol study (NCT02884102) enrolled 228 cases of multiple myeloma that were molecularly profiled using clinical-grade sequencing performed on the Michigan Oncology Sequencing platform. For each case, a molecular report was produced that highlighted actionable findings.

Among the total enrollment population, 84% of the sequenced samples (n = 192) relayed very good tumor content and 76% were found to harbor at least on potentially actionable alteration. Among those cases, 53% had alterations in the MAPK pathway, 14% in the CCND1 and cyclin-dependent kinase pathway, and 6% had activating FGFR3 mutations.

Researchers reported that 10% of all cases presented with mutational signatures in both bone marrow aspirates and matched peripheral blood of genes associated with MDS, AML, as well as other myeloid disorders.


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Researchers concluded that actionable alterations are likely identifiable in a majority of multiple myeloma cases and that deep sequencing of both bone marrow aspirates and normal blood could help identify events that would be missed if sequencing is only performed on the marrow. “Although clinical applicability has been limited so far by the lack of availability of targeted agents for myeloma patients, the results suggest that precision medicine approaches in multiple myeloma are possible and should be further studied clinically,” they wrote.

A master protocol (MyDRUG) has since been launched for developing new multiple myeloma regimens based on individual genomic landscapes.—Zachary Bessette