Selective Inhibition of Nuclear Export in Heavily Pretreated Relapsed or Refractory Multiple Myeloma
In a phase II trial reported in the Journal of Clinical Oncology, Vogl et al found that the investigational oral selective exportin 1 (XPO1) inhibitor selinexor combined with dexamethasone produced responses in patients with heavily pretreated relapsed or refractory multiple myeloma.
Selinexor induces apoptosis in cancer cells via nuclear retention of tumor-suppressor proteins and the glucocorticoid receptor and inhibits translation of oncoprotein microRNAs.
Study Details
In the multicenter study, 48 patients had quad-refractory disease (ie, refractory to bortezomib, carfilzomib [Kyprolis], lenalidomide [Revlimid], and pomalidomide [Pomalyst]), and 30 evaluable patients had penta-refractory disease (ie, also refractory to an anti–CD38 antibody). All 78 patients were treated with selinexor at 80 mg and dexamethasone at 20 mg twice weekly in 28-day cycles. They had received a median of seven prior regimens. The primary endpoint was overall response rate.
Response Rates
A response was observed in 16 patients (21%), including 21% of those with quad-refractory and 20% of those with penta-refractory disease. Among 17 patients with high-risk cytogenetics, including t(4;14), t(14;16), and del(17p), a response was observed in 6 (35%). The median duration of response was 5 months; 65% of responding patients remained alive at 12 months.
Adverse Events
The most common grade ≥ 3 adverse events were thrombocytopenia (59%), anemia (28%), neutropenia (23%), hyponatremia (22%), leukopenia (15%), and fatigue (15%). Adverse events led to dose interruption in 52% of patients, dose reduction in 37%, and treatment discontinuation in 18%.
The investigators concluded, “The combination of selinexor and dexamethasone has an [overall response rate] of 21% in patients with heavily pretreated, refractory myeloma with limited therapeutic options.”
The study was supported by Karyopharm Therapeutics.
Dan T. Vogl, MD, of the Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, is the corresponding author for the Journal of Clinical Oncology article.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
