The Food and Drug Administration (FDA) has approved Xpovio® (selinexor; Karyopharm) in combination with bortezomib and dexamethasone for the treatment of adults with multiple myeloma who have received at least 1 prior therapy.
The approval was based on data from the randomized, open-label phase 3 BOSTON trial that assessed the efficacy and safety of selinexor in combination with bortezomib and dexamethasone in 402 adults with relapsed or refractory multiple myeloma who had received 1 to 3 prior therapies. Patients were randomized 1:1 to receive either selinexor 100mg orally once weekly plus bortezomib and dexamethasone (SVd) or bortezomib and dexamethasone (Vd).
Results demonstrated that SVd-treated patients met the primary end point achieving a significantly longer median progression-free survival of 13.9 months (95% CI, 11.7, not reached) vs 9.5 months (95% CI, 7.6-10.8) for Vd (hazard ratio 0.70; 95% CI, 0.53-0.93; P =.0075). Moreover, a significantly greater overall response rate was observed with SVd compared with Vd (76.4% vs 62.3%; P =.0012). Patients in the SVd arm were found to have a higher rate of very good partial response or better compared with Vd (44.6% vs 32.4%; P =.0082). Among responders, the median duration of response was 20.3 months for SVd and 12.9 months for Vd.
Adverse reactions reported most frequently with selinexor included fatigue, nausea, decreased appetite, diarrhea, peripheral neuropathy, upper respiratory tract infection, decreased weight, cataract and vomiting. In the BOSTON study, peripheral neuropathy rates of grade 2 or above were found to be significantly lower with SVd (21%) compared with Vd (34%; odds ratio 0.50; 95% CI, 0.32-0.79; P =.0013). The most common grade 3‐4 laboratory abnormalities included thrombocytopenia, lymphopenia, hypophosphatemia, anemia, hyponatremia and neutropenia.
Commenting on the approval, Paul Richardson, MD, Clinical Program Leader and Director of Clinical Research, Jerome Lipper Multiple Myeloma Center at Dana-Farber Cancer Institute and co-senior author of the BOSTON study publication, said: “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 multiple myeloma patients in need of new therapeutic options.”
Xpovio is already indicated in combination with dexamethasone for the treatment of adults with relapsed or refractory multiple myeloma who underwent at least 4 prior therapies and whose disease was refractory to at least 2 proteasome inhibitors, at least 2 immunomodulatory agents, and an anti-CD38 monoclonal antibody.
It is also approved for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least 2 lines of systemic therapy.
For more information visit xpovio.com.
- Karyopharm announces FDA approval of Xpovio® (selinexor) as a treatment for patients with multiple myeloma after at least one prior therapy. [press release]. Newton, MA: Karyopharm Therapeutics Inc.; December 18, 2020.
- Xpovio [package insert]. Newton, MA: Karyopharm Therapeutics Inc.; 2020.