Dr. Friedman on the Mechanism of Action of Selinexor in Multiple Myeloma

Robb S. Friedman, MD, a hematologist and oncologist at Massachusetts General Hospital, discusses the mechanism of action of selinexor (Xpovio) in multiple myeloma.

Selinexor is a first-in-class selective inhibitor of nuclear export that targets XPO1, which is a protein that is overexpressed on myeloma cells, says Friedman.

In July 2019, the FDA granted an accelerated approval to selinexor for use in combination with dexamethasone for the treatment of patients with relapsed/refractory multiple myeloma who received ≥4 prior therapies and whose disease is refractory to ≥2 proteasome inhibitors, ≥2 immunomodulatory agents, and a CD38-targeted monoclonal antibody.

Selinexor prevents the exportation of messenger RNA from reaching the nucleus of oncogenic proteins that make cells malignant, says Friedman.

The agent has shown marked activity in multiple myeloma. By inhibiting XPO1, the myeloma cells undergo apoptosis, concludes Friedman.