Dr. Cristina Gasparetto on the Results of Once-weekly Xpovio (selinexor), Kyprolis (carfilzomib), and dexamethasone, or (XKd)
Background of the Study:
Exportin 1 (XPO1) mediates the nuclear export and functional inactivation of tumor suppressor proteins (TSPs), is associated with poor prognosis in MM, and contributes to proteasome inhibitor (PI) and immunomodulatory drug (IMiD) resistance. Selinexor (SEL) is a novel, oral, first-in-class selective inhibitor of nuclear export (SINE) compound that blocks XPO1, forcing the nuclear retention and activation of TSPs. SEL in combination with low dose dexamethasone (dex) ± bortezomib (BOR) is FDA approved for previously treated MM. The synergy of SEL with the PI BOR has been confirmed in the phase 3 BOSTON study in MM patients (pts) with 1-3 prior therapies; once weekly (QW) SEL, QW BOR, and dex (XVd) significantly increased progression-free survival (PFS), time to next therapy, and overall response rate (ORR) as compared to standard twice weekly BOR/dex (Vd), despite XVd using 40% less BOR and 25% less dex than standard Vd.
In this video:
Dr. Cristina Gasparetto (Duke Medical Center, Durham, NC) discusses the results of once weekly Xpovio (selinexor), Kyprolis (carfilzomib), and dexamethasone (XKd) in heavily pretreated multiple myeloma.
Conclusions:
In patients with heavily pretreated MM, weekly XKd is highly active with an overall response rate (ORR) of 78% and deep responses (≥Very Good Partial Response 48%) with an overall progression-free survival of 23 months. All adverse events including grade 3/4 thrombocytopenia can be managed with appropriate supportive care and dose modifications. These data support further investigation of XKd in patients with previously treated multiple myeloma including those previously treated with dara.
