December 18, 2020
2 min read
The FDA approved selinexor as part of a three-agent regimen for adults with multiple myeloma who received at least one prior therapy.
The approval applies to use of selinexor (Xpovio, Karyopharm Therapeutics) in combination with bortezomib (Velcade, Millennium/Takeda) and dexamethasone.
Selinexor is a first-in-class, oral selective inhibitor of nuclear export compound. The drug binds with and inhibits the nuclear export protein XPO1, leading to the accumulation of tumor suppressor proteins in the cell nucleus.
The FDA previously granted accelerated approval to selinexor for treatment of adults with relapsed or refractory multiple myeloma who received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents and an anti-CD38 monoclonal antibody.
“[This] approval broadens the existing label for Xpovio and allows Karyopharm to offer a new, highly active treatment option to a significantly expanded patient population,” Sharon Shacham, PhD, MBA, founder, president and chief scientific officer of Karyopharm Therapeutics, said in a company-issued press release. “We believe the expanded reach of Xpovio will address a critical need for patients with multiple myeloma given its novel mechanism of action, convenient oral administration and established rapid and sustained efficacy profile.”
The FDA based the label expansion on results of the randomized phase 3 BOSTON study, which included 402 adults with relapsed or refractory multiple myeloma who received one to three prior lines of therapy.
Researchers randomly assigned patients in the experimental group to once-weekly selinexor in combination with once-weekly bortezomib plus low-dose dexamethasone. Patients in the control group received twice-weekly bortezomib plus dexamethasone.
PFS served as the primary endpoint. Key secondary endpoints included overall response rate and rate of peripheral neuropathy.
Researchers reported longer PFS (median, 13.9 months vs. 9.5 months; HR = 0.7; P = .0075) and a higher ORR (76.4% vs. 62.3%; P = .0012) in the selinexor group.
Results showed a significantly lower rate of peripheral neuropathy with the selinexor regimen (any grade, 32% vs. 47%; grade 2 or higher, 21% vs. 34%).
The most common adverse events reported in the selinexor group included cytopenias, along with gastrointestinal and constitutional symptoms.
The most common nonhematologic adverse events — most of which were grade 1 or grade 2 — included fatigue (59%), nausea (50%), decreased appetite (35%) and diarrhea (32%).
The most common grade 3 or grade 4 adverse events included thrombocytopenia (43%), lymphopenia (38%), fatigue (28%) and anemia (17%).
Paul G. Richardson
“New treatments for multiple myeloma remain a critical need for both patients and their treating physicians,” study investigator Paul G. Richardson, MD, clinical program leader and director of clinical research at Jerome Lipper Multiple Myeloma Center at Dana-Farber Cancer Institute, as well as a HemOnc Today Editorial Board Member, said in the release. “As the only approved nuclear export inhibitor that has demonstrated a strong synergistic effect with a proteasome inhibitor such as bortezomib, selinexor has, in my opinion, the potential to meet a current treatment gap for our [patients with multiple myeloma] in need of new therapeutic options.”
The FDA previously approved selinexor for treatment of certain adults with relapsed or refractory diffuse large B-cell lymphoma who received at least two prior lines of systemic therapy.