Despite a high rate of grade 3 to 4 adverse events (AEs), selinexor showed promising clinical activity among heavily pretreated patients with multiple myeloma, according to a study published in the Journal of Clinical Oncology.1
Patients with quad- or penta-refractory myeloma have limited treatment options. Selinexor, an orally administered selective inhibitor of exportin 1 (XPO1), previously showed anti-myeloma activity in a phase 1 trial.
Of 79 patients enrolled to this phase 2 trial, 48 had quad-refractory (to bortezomib, carfilzomib, lenalidomide, and pomalidomide) and 31 had penta-refractory (to the aforementioned 4 and an anti-CD38 antibody) disease. All patients received selinexor 80 mg and dexamethasone 20 mg twice weekly.
The overall median age was 63 years, the median number of years since diagnosis was 4 (range, 3-17), and 56% of the 39 patients with cytogenetic assessments had standard-risk cytogenetics.
Seventy-eight patients were included in the efficacy analysis. The overall response rate was 21% (21% among patients with quad-refractory disease and 20% among patients with penta-refractory disease). Four patients had a very good partial response, 12 patients had a partial response, 10 patients had a minimal response, and 27 had stable disease.
Among the 17 patients with high-risk cytogenetics, the overall response rate was 35%.
The median progression-free survival was 2.3 months; median overall survival was 9.3 months.
The rate of grade 3 to 4 AEs was, however, high: 59% of patients had grade 3 or 4 thrombocytopenia, 23% of patients had grade 3 or 4 neutropenia, and 28% of patients had grade 3 or 4 anemia. Fourteen patients discontinued treatment.
The authors concluded that “selinexor is an oral agent with a novel mechanism of action and evidence of antimyeloma efficacy. In combination with low-dose dexamethasone, selinexor is an effective therapy for patients with refractory multiple myeloma for whom available treatments have been exhausted.”
- Vogl DT, Dingli D, Cornell RF, et al. Selective inhibition of nuclear export with oral selinexor for treatment of relapsed or refractory multiple myeloma. J Clin Oncol. 2018 Jan 30. doi: 10.1200/JCO.2017.75.5207 [Epub ahead of print]