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The European Medicines Agency’s Committee for Medicinal Products for Human Use has recommended the approval of selinexor in combination with bortezomib and low-dose dexamethasone for use in adult patients with multiple myeloma who have previously received 1 to 3 prior lines of treatment.
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended the approval of selinexor (Nexpovio) in combination with bortezomib (Velcade) and low-dose dexamethasone (SVd) for use in adult patients with multiple myeloma who have previously received 1 to 3 prior lines of treatment.1
The positive opinion is based on findings from the phase 3 BOSTON study (NCT03110562), in which the regimen (n = 402) resulted in a median progression-free survival (PFS) of 13.93 months (95% CI, 11.73–not evaluable [NE]) vs 9.46 months (95% CI, 8.11-10.78) with bortezomib/dexamethasone alone (n = 207) in this population (HR, 0.70; 95% CI, 0.53-0.93; P = .0075).2
The European Commission is expected to decide on the selinexor application within approximately 60 days after the recommendation.
“Despite therapeutic advances, multiple myeloma remains an incurable disease that is difficult to treat,” Richard Paulson, president and chief executive officer of Karyopharm Therapeutics, Inc., stated in a press release. “Today’s positive CHMP opinion brings us 1 step closer to our goal of making [selinexor] available to patients globally who may benefit from this novel mechanism of action. We are pleased to have Menarini as a partner in this effort given its commercialization expertise as well as strong heritage and footprint in Europe.”
The open-label, randomized phase 3 trial enrolled patients with multiple myeloma who were 18 years of age or older who have measurable disease and documented disease progression on or following the most recent regimen received. Patients needed to have received 1 prior therapy but no more than 3 regimens; they also needed to have an ECOG performance status of 0 to 2, and acceptable hepatic, renal, and hematopoietic function.
If patients had systemic light-chain amyloidosis, central nervous system involvement, or grade 2 or higher peripheral neuropathy, they were excluded.
Study participants were randomized 1:1 to receive selinexor, bortezomib, and dexamethasone or bortezomib and dexamethasone alone. Those in the investigative arm received oral selinexor at a fixed dose of 100 mg on days 1, 8, 15, 22, and 29 of each 5-week cycle; subcutaneous bortezomib at a once weekly dose of 1.3 mg/m2 on days 1, 8, 15, and 22 of each cycle; and oral dexamethasone at 20 mg on days 1, 2, 8, 9, 15, 16, 22, 23, 29, and 30 of each cycle.
The primary end point of the trial was PFS, and secondary end points included objective response rate (ORR), overall survival, duration of response, progression-free survival, and ORR in those who crossed over from the control arm to the investigative arm.
Other end points included PFS on the subsequent line of therapy, time to next treatment, time to response, incidence of grade 2 or higher neuropathy effects, as well as safety and tolerability.
Baseline demographic, disease, and clinical characteristics were well balanced between the arms.
At a data cutoff of February 18, 2020, 19% of those in the investigative arm vs 17% of those on the control arm were still receiving treatment. Most patients discontinued due to disease progression (34% vs 52%, respectively).
The median follow-up was 13.2 months (IQR, 6.2-19.8) in the selinexor arm and 16.5 months (IQR, 9.4-19.8) in the control arm. Data showed that the ORR was significantly higher with the selinexor combination vs the control regimen, at 76.4% (95% CI, 69.8%-82.2%) and 62.3% (95% CI, 55.3%-68.9%), respectively (odds ratio [OR], 1.96; 95% CI, 1.3-3.1; P = .0012). Moreover, a higher proportion of patients in the investigative arm experienced a very good partial response or better vs the control arm (OR, 1.66; 95% CI, 1.1-2.5; P = .0082).
The median time to first response in those who received selinexor was 1.1 months (IQR, 0.8-1.6) vs 1.4 months (IQR, 0.8-1.6) in those who did not. Median DOR was 20.3 months (95% CI, 12.5-NE) vs 12.9 months (95% CI, 9.3-15.8), respectively (HR, 0.81; 95% CI, 0.56-1.17; P = .1364). The median time to next treatment was longer among those in the investigative arm vs the control arm, at 16.1 months vs 10.8 months, respectively (HR, 0.66; 95% CI, 0.50-0.86; P = .0012).
A total of 195 patients in the selinexor arm and 204 in the control arm comprised the safety population for the trial. The most common grade 3 or 4 treatment-emergent toxicities included thrombocytopenia, anemia, pneumonia, and fatigue; the incidence of these effects was higher in the selinexor arm vs the control arm.