The FDA has approved selinexor in combination with bortezomib and dexamethasone (Vd) for the treatment of adults with multiple myeloma (MM) who have received at least one prior therapy.
Selinexor is an oral selective inhibitor of nuclear export (SINE). The approval decision is based on results from the phase III BOSTON trial, which compared the efficacy and safety of once-weekly selinexor plus Vd (SVd) versus twice-weekly Vd among 402 adult patients with relapsed or refractory MM who had received one to three prior lines of therapy.
The median progression-free survival (PFS) in the SVd arm was 13.9 months, compared with 9.5 months in the Vd arm, representing a 47% improvement in PFS. Participants in the SVd arm also had a significantly higher overall response rate (76.4% vs. 62.3%; odds ratio = 1.96; p=0.0012). Investigators noted that higher response rates were observed regardless of prior therapies received, the presence of high-risk cytogenetics, renal impairment, or advanced age.
Cytopenias were the most common AEs, followed by gastrointestinal and constitutional symptoms. The most common nonhematologic AEs included fatigue (59%), nausea (50%), decreased appetite (35%), and diarrhea (32%). The most common grade 3/4 AEs were thrombocytopenia (43%), lymphopenia (38%), fatigue (28%), and anemia (17%). Most AEs were manageable with dose modifications or standard supportive care.
SVd also was associated with improvements in certain health-related quality-of-life measurements, including 35% fewer clinic visits compared with the Vd regimen.
Earlier in 2020, selinexor was granted accelerated approval for patients with relapsed/refractory MM who have received four or more prior therapies and whose disease has not responded to treatment with two or more proteasome inhibitors or immunomodulatory agents based on data from the single-arm, phase II STORM trial. The FDA’s Oncologic Drugs Advisory Committee raised concerns about this decision and recommended against approval until results from the BOSTON trial became available.
Source: Karyopharm press release, December 18, 2020.