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Blood. 2018 Dec 13;132(24):2546-2554. doi: 10.1182/blood-2018-06-858852. Epub 2018 Oct 23.

Selinexor plus low-dose bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma.

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Charbonneau Cancer Research Institute, Calgary, AB, Canada.
Vancouver General Hospital, Vancouver, BC, Canada.
QEII Health Sciences Center, Dalhousie University, Halifax, NS, Canada.
Royal Victoria Hospital, Montreal, QC, Canada.
Multiple Myeloma and Amyloidosis Service, Columbia University, New York, NY.
Cancer Centre Manitoba, Winnipeg, MB, Canada.
Cross Cancer Institute, University of Alberta, Edmonton, AB, Canada.
Duke University Cancer Center, Durham, NC.
Myeloma Canada, Dorval, QC, Canada.
Princess Margaret Cancer Center, Toronto, ON, Canada; and.
Karyopharm Therapeutics Inc, Newton, MA.


Selinexor is an oral inhibitor of the nuclear export protein exportin 1. Preclinical studies demonstrated synergistic antimyeloma activity between selinexor and proteasome inhibitors (PI) through suppression of NF-κB signaling and nuclear retention of tumor suppressor proteins. We tested selinexor in combination with low-dose bortezomib and dexamethasone (SVd) for the treatment of relapsed or refractory multiple myeloma (MM). The primary objectives of this study were to determine the safety profile, overall response rate (ORR), and a recommended phase 2 dose (RP2D) of SVd. We enrolled 42 patients to receive selinexor (60, 80, or 100 mg orally) plus bortezomib (1.3 mg/m2 subcutaneously) and dexamethasone (20 mg orally) once or twice weekly in 21- or 35-day cycles. Patients had a median of 3 (range 1-11) prior lines of therapy, and 50% were refractory to a PI. Treatment-related grade 3 or 4 adverse events reported in ≥10% of patients were thrombocytopenia (45%), neutropenia (24%), fatigue (14%), and anemia (12%). Incidence (4 patients, 10%) and grade (≤2) of peripheral neuropathy were low. The ORR for the entire population was 63%: 84% ORR for PI nonrefractory and 43% for PI-refractory patients. The median progression-free survival for all patients was 9.0 months; 17.8 months for PI nonrefractory, and 6.1 months for PI refractory. SVd treatment produced high response rates in patients with relapsed or refractory MM, including borezomib-refractory MM, with no unexpected side effects. The RP2D is selinexor (100 mg once weekly), bortezomib (1.3 mg/m2 once weekly for 4 weeks), and dexamethasone (40 mg once weekly) per 35-day cycle. This trial was registered at as #NCT02343042.

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