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 www.clinicaltrials.gov as 
#NCT02343042.