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The European Commission granted a full marketing authorization to selinexor in combination with once-weekly bortezomib and low-dose dexamethasone for the treatment of adults with multiple myeloma who have received at least 1 previous therapy.
The European Commission granted a full marketing authorization to selinexor (Nexpovio) in combination with once-weekly bortezomib (Velcade) and low-dose dexamethasone (SVd) for the treatment of adults with multiple myeloma who have received at least 1 previous therapy.1
With this decision, which follows the positive opinion granted by the European Medicines Agency’s Committee for Medicinal Products for Human Use in May 2022,2 the conditional marketing authorization of selinexor has been converted to a full approval.
The approval is supported by findings from the phase 3 BOSTON study (NCT03110562), in which the combination (n = 402) resulted in a median progression-free survival (PFS) of 13.93 months (95% CI, 11.73–not evaluable [NE]) compared with 9.46 months (95% CI, 8.11-10.78) with bortezomib plus dexamethasone alone (n = 207) in this population (HR, 0.70; 95% CI, 0.53-0.93; P = .0075).3
“The European Commission’s approval of an expanded use of [selinexor] provides another option for patients with multiple myeloma who have relapsed, or become resistant to current treatment regimens,” Richard Paulson, president and chief executive officer of Karyopharm Therapeutics, Inc., stated in a press release. “Our decision to pursue approval for this patient population is indicative of our commitment to expand access to selinexor across the globe and we look forward to working closely with Menarini who will commercialize [selinexor] in Europe.”
Patients with multiple myeloma who were at least 18 years of age, had measurable disease, and documented disease progression on or following the most recent regimen received were enrolled to the BOSTON trial. To be eligible, patients were required to have received 1 previous therapy, but no more than 3 regimens. They also needed to have an ECOG performance status ranging from 0 to 2, and adequate hepatic, renal, and hematopoietic function.
Exclusion criteria included having systemic light-chain amyloidosis, central nervous system involvement, or peripheral neuropathy that was grade 2 or higher in severity.
Patients were randomly assigned 1:1 to receive the selinexor combination or bortezomib/dexamethasone alone. Oral selinexor was administered at a fixed dose of 100 mg on days 1, 8, 15, 22, and 29 of each 5-week treatment cycle. Bortezomib was given subcutaneously at a dose of 1.3 mg/m2 once weekly on days 1, 8, 15, and 22 of each cycle. Lastly, oral dexamethasone was delivered at a dose of 20 mg on days 1, 2, 8, 9, 15, 16, 22, 23, 29, and 30 of each treatment cycle.
PFS served as the primary end point of the trial. Secondary end points comprised objective response rate (ORR), duration of response and overall survival. In those who crossed over from the control arm to the investigative arm, PFS and ORR was also examined. Other end points of interest included PFS on the subsequent line of therapy, time to next treatment, time to response, incidence of grade 2 or higher neuropathy effects, safety, and tolerability.
Demographic, disease, and clinical characteristics at baseline were noted to be well balanced between the treatment arms.
At the February 18, 2020, data cutoff date, 19% of those in the selinexor arm vs 17% of those in the control arm were still receiving treatment. The majority of patients on both arms who discontinued treatment did so because of progressive disease, at 34% and 52%, respectively.
In the selinexor arm, the median follow-up was 13.2 months (interquartile range [IQR], 6.2-19.8); in the control arm, the median follow-up was 16.5 months (IQR, 9.4-19.8).
Additional findings indicated that the ORR achieved with the selinexor combination was 76.4% (95% CI, 69.8%-82.2%) vs 62.3% (95% CI, 55.3%-68.9%) with the control doublet (odds ratio [OR], 1.96; 95% CI, 1.3-3.1; P = .0012). More patients in the investigative arm achieved a very good partial response or better compared with those on the control arm (OR, 1.66; 95% CI, 1.1-2.5; P = .0082).
Additionally, the median time to first response with the selinexor combination was 1.1 months (IQR, 0.8-1.6) vs 1.4 months (IQR, 0.8-1.6) with the control regimen. The median DOR in the investigative and control arms was 20.3 months (95% CI, 12.5-NE) and 12.9 months (95% CI, 9.3-15.8), respectively (HR, 0.81; 95% CI, 0.56-1.17; P = .1364). Moreover, the median time to next treatment was reported to be longer in those who received selinexor vs those who did not, at 16.1 months vs 10.8 months, respectively (HR, 0.66; 95% CI, 0.50-0.86; P = .0012).
Regarding safety, investigators evaluated 195 patients in the selinexor arm and 204 patients in the control arm. The most frequently experienced grade 3 or 4 treatment-emergent toxicities with the regimen included thrombocytopenia, anemia, pneumonia, and fatigue. The incidence of these adverse effects was noted to be higher with the selinexor regimen vs the control regimen.