Selinexor in combination with bortezomib and dexamethasone approved for relapsed/refractory multiple myeloma

On December 18, 2020, the U.S. Food and Drug Administration (FDA) approved the combination of selinexor plus bortezomib and dexamethasone in adult patients with multiple myeloma (MM) after at least one prior therapy.¹

Selinexor is an XPO1 inhibitor indicated in the treatment of penta-refractory MM. The FDA approved selinexor with dexamethasone in July 2019 for patients refractory to at least two immunomodulatory agents, two proteasome inhibitors, and an anti-CD38 monoclonal antibody, based on the response rate achieved in the STORM study (NCT02336815). However, during selinexor’s review, the FDA oncologic drugs advisory committee recommended delaying the accelerated approval until data were available from the phase III BOSTON trial (NCT03110562) on selinexor plus bortezomib and dexamethasone.

Results from the BOSTON trial, reported at this year’s virtual American Society of Clinical Oncology Annual Meeting and recently published in Lancet,² indicate that once-weekly selinexor plus bortezomib and low-dose dexamethasone twice-weekly was more effective in patients with MM who have received one to three previous lines of therapy, compared with the standard twice-weekly bortezomib plus low-dose dexamethasone. The median progression-free survival was 13.9 months (95% CI, 11.7–not estimable) vs 9.5 months (95% CI, 8.1─10.8; HR, 0.70 [95% CI, 0.53─0.93]; p = 0.0075), in patients treated with selinexor, bortezomib, and dexamethasone vs those treated with bortezomib and dexamethasone.²

The most frequent Grade 3–4 adverse events were thrombocytopenia, fatigue, anemia, and pneumonia. Peripheral neuropathy of Grade ≥ 2 was less frequent with selinexor, bortezomib, and dexamethasone than with bortezomib and dexamethasone (21% vs 34%; odds ratio, 0.50; 95% CI, 0.32–0.79; p = 0.0013).²

The recommended doses are as follows¹:

• Selinexor, 100 mg orally once weekly on day 1 of each week of a 35-day cycle until disease progression or unacceptable toxicity.
• Bortezomib 1.3 mg/m² subcutaneously once weekly on day 1 of each week for 4 weeks followed by 1 week off.
• Dexamethasone, 20 mg orally twice weekly on days 1 and 2 of each week.

The full prescribing information can be found here.