FoundationOne Heme identifies clinically actionable genomic alterations in multiple myeloma cases

Foundation Medicine today announced new data from a pilot study demonstrating that its fully informative genomic profile for hematologic malignancies, FoundationOne™ Heme, identified both novel and previously reported clinically actionable genomic alterations in multiple myeloma cases. These data were presented in an oral presentation titled Pilot Study To Evaluate The Prevalence Of Actionable Oncogenic Mutations In Patients With Relapsed Refractory Multiple Myeloma (abstract number 755) by Alexander Lesokhin, M.D., medical oncologist, Memorial Sloan-Kettering Cancer Center, at the 55^th American Society of Hematology Annual Meeting in New Orleans.

"Multiple myeloma is a treatable, but ultimately incurable, blood cancer that eventually becomes resistant to all currently available therapies," said Dr. Lesokhin. "Advances in clinical next-generation sequencing have made it possible to rapidly identify genomic alterations that may be driving a patient's cancer and could inform treatment options leading to advances in clinical development of new targeted therapies in multiple myeloma patients."

In this study, researchers at Memorial Sloan-Kettering used FoundationOne Heme to analyze whole bone marrow aspirate samples from 28 newly diagnosed and 27 heavily pre-treated multiple myeloma patients. High coverage and high quality sequence data was obtained in 98% (54/55) of cases, and alteration prevalence was examined in 63% of (35/55) samples with sufficient plasma cell content. In the analysis:

• A high frequency of alterations in the MAPK pathway was observed, including mutually exclusive alterations in NRAS and KRAS in 48% of cases, and BRAF V600E alteration in 3% of cases.
• Fourteen percent of cases had TET2 frameshift/nonsense alterations or IDH2 alterations, suggesting the DNA hydroxymethylation pathway is targeted by recurrent somatic alterations in multiple myeloma.
• Alterations in epigenetic modifiers were identified in 41% of cases, including alterations in TET2/IDH, chromatin modifying enzymes/scaffolds (ARID1A, ASXL1) and DNA methyltransferases (DNMT3A).
• Novel alterations in DNA repair pathways (ATM, FANCA, FANCD2) and in FAT3 were identified, suggesting there are novel disease alleles which require functional investigation for their role in multiple myeloma pathogenesis.

"These data support the clinical utility of FoundationOne Heme and the benefit of our comprehensive genomic profiling approach in identifying oncogenic drivers in multiple myeloma," said Vincent Miller, M.D., chief medical officer, Foundation Medicine. "MEK/RAF inhibition has demonstrated clinical efficacy in a range of cancers and there are emerging data that epigenetic and targeted therapies may provide benefit in patients with TET2/IDH mutations. Therefore, these results demonstrate that FoundationOne Heme can identify clinically actionable alterations that may support the clinical development of new treatment options and advance precision medicine for multiple myeloma patients."