Selinexor in Combination with SVd Induces a High Response Rate in Patients with RMM
Description: Selinexor in Combination with Weekly Low Dose Bortezomib and Dexamethasone (SVd) Induces a High Response Rate with Durable Responses in Patients with Refractory Multiple Myeloma (MM)
Nizar J. Bahlis, MD
Southern Alberta Cancer Research Institute
Calgary, AB, Canada
Background: Selinexor is a first-in-class Selective Inhibitor of Nuclear Export (SINE) compound that binds and inactivates Exportin 1 (XPO1). Twice weekly (BIW) bortezomib in combination with dexamethasone (Vd) is an established therapy in relapsed and refractory multiple myeloma (RRMM). While the activity of bortezomib (bort) BIW in combination with other agents is efficacious, prolonged use is limited due to peripheral neuropathy (50-60%) as well as acquired resistance to bort. Strategies to identify new dosing regimes with high response rates, improved tolerability and the ability to overcome resistance are needed. Preclinical studies have shown that selinexor, when combined with bort, can restore sensitivity of bort-resistant MM, inhibiting tumor growth and increasing survival in murine MM xenografts. In this clinical trial (NCT02343042), we investigated the safety, tolerability and efficacy of the combination of selinexor, bortezomib and low dose dexamethasone (SVd) in patients (pts) with RRMM.