24 June 2022

Genes that predict a good response to a new multiple myeloma therapy have been identified for the first time.

Selinexor has been shown to be beneficial for people with multiple myeloma for whom other therapies have not been effective. However, scientists have been unable to identify which patients would benefit the most. This is important because most patients who take the drug experience side-effects, sometimes severe. 

Now, researchers at Mount Sinai in New York, USA, have identified a signature of three genes – WNT10A, DUSP1, and ETV7 – after sequencing RNA of multiple myeloma tumours from about 100 patients treated with selinexor. Patients who had high levels of activity in these three genes had longer progression-free survival or better depth of response.

The team validated the signature in an independent group of patients who participated in an international clinical trial called STORM that led to the US Food and Drug Administration (FDA) approval of the drug.

The team also found the three-gene signature in patients with the brain cancer glioblastoma who responded well to selinexor. The findings are published in JCO Precision Oncology.

Senior author Dr Alessandro Laganà from Mount Sinai, said: “This signature has important clinical significance, as it could identify patients who are most likely to benefit from treatment with selinexor-based therapy, especially in earlier lines of therapy.”

Fellow senior author Dr Samir Parekh from Mount Sinai added: “Our findings provide the basis for improving patient selection for targeted agents using a small panel of genes to guide precise application of these drugs in real world scenarios, including relapse following CAR-T, an increasingly important clinical challenge in myeloma.”

Source: Restrepo P, Bhalla S, Ghodke-Puranik Y, Aleman A, Leshchenko V, Melnekoff DT, Agte S, Jiang J, Madduri D, Richter J, Richard S, Chari A, Cho HJ, Jagannath S, Walker CJ, Landesman Y, Laganà A, Parekh S.  (2022) “A Three-Gene Signature Predicts Response to Selinexor in Multiple Myeloma.” JCO Precision Oncology, doi: 10.1200/PO.22.00147.  

Link: https://ascopubs.org/doi/full/10.1200/PO.22.00147

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