EHA 2018: Selinexor and Bortezomib Combination in Resistant Multiple Myeloma
Posted: Wednesday, June 27, 2018
A combination of selinexor, a first-in-class selective inhibitor of nuclear export (SINE), low-dose bortezomib, and dexamethasone given weekly appears to be well tolerated and active in patients with relapsed or refractory multiple myeloma. Nizar Bahlis, MD, of the Southern Alberta Cancer Research Institute in Calgary, Canada, and colleagues presented updated clinical data from one arm of the STOMP study at the 2018 European Hematology Association (EHA) Annual Congress in Stockholm (Abstract PS1322).
Currently, use of protocols that include bortezomib are limited due to the risk of peripheral neuropathy (observed in between 50% and 60% of patients) and acquired resistance. Therefore, new regimens with improved tolerability are needed, reasoned the investigators.
The phase Ib/II study enrolled 42 patients with proteasome inhibitor–naive, exposed or refractory disease in the dose-escalation (n = 22) and dose-expansion (n = 20) cohorts. Based on tolerability and efficacy, the recommended phase II dosing of selinexor is 100 mg; bortezomib, 1.3 mg/m2; and dexamethasone, 40 mg—all given weekly.
In the proteasome inhibitor–relapsed or –naive population (n = 19), the overall response rate was 84%, with a median progression-free survival of 17.8 months. In patients with proteasome inhibitor–refractory multiple myeloma (n = 21), the overall response rate of 43% and the clinical benefit rate of 67% “support preclinical findings that selinexor re-sensitizes and overcomes resistance to [proteasome inhibitors],” the investigators concluded.
The regimen was well tolerated, with no overt major organ toxicities observed. According to Dr. Bahlis and colleagues, peripheral neuropathy was seen in 6 patients (14%), 5 of whom had prior exposure to bortezomib.
