MHRA Approves Selinexor Plus Bortezomib/Dexamethasone for Multiple Myeloma Following 1 Prior Therapy

The United Kingdom’s Medicines and Healthcare Products Regulatory Agency (MHRA) has granted full marketing authorization for selinexor (Nexpovio; Xpovio) in combination with bortezomib (Velcade) and low-dose dexamethasone (SVd) for the treatment of adult patients with multiple myeloma who have received at least 1 prior therapy.¹

The regulatory decision was supported by findings from the phase 3 BOSTON trial (NCT03110562), which demonstrated a statistically significant reduction in the risk of disease progression or death compared with bortezomib and dexamethasone alone (Vd). At a median follow-up of 13.2 months (interquartile range [IQR], 6.2-19.8) for the SVd arm and 16.5 months (IQR, 9.4-19.8) for the Vd arm, patients treated with SVd experienced a median progression-free survival (PFS) of 13.93 months (95% CI, 11.73–not evaluable) compared with 9.46 months (95% CI, 8.11-10.78) for those given Vd (HR, 0.70; 9%% CI, 0.53-0.93; P = .0075).²

“Receiving full marketing authorization from the MHRA marks another significant milestone for [selinexor],” Richard Paulson, MBA, president and chief executive officer of Karyopharm Therapeutics, the developer of selinexor, stated in a news release. “We are thrilled to expand the positive impact of [selinexor] to people living with multiple myeloma across Great Britain and continue working to further broaden access to selinexor across the globe.”

Previously, in December 2020, the FDA approved selinexor in combination with bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least 1 previous therapy.³ The FDA’s decision was also based on findings from the BOSTON trial.

The multicenter, randomized phase 3 BOSTON study evaluated 402 adult patients with relapsed/refractory multiple myeloma who received 1 to 3 lines of prior therapy, including proteasome inhibitors.²

Patients were randomly assigned 1:1 to received selinexor at 100 mg once weekly plus bortezomib at 1.3 mg/m² once weekly and dexamethasone at 20 mg 4 times per week for the first 24 weeks and twice per week thereafter, or bortezomib and dexamethasone alone on the same dosing schedule.

PFS in the intention-to-treat population served as the study’s primary end point. Key secondary end points included overall response rate (ORR), overall survival (OS), duration of response (DOR), time to next treatment, time to response, rate of peripheral neuropathy, and safety.⁴

Additional data showed that patients in the SVd arm achieved an ORR of 76.4%, vs 62.3% for those in the Vd arm (P = .0012).⁵ Furthermore, 44.6% of patients in the SVd group experienced a very good partial response or better compared with 32.4% in the Vd group. The complete response (CR)/stringent CR rates were 16.9% and 10.6% in the SVd and Vd arms, respectively. The median duration of response was 20.3 months with the addition of selinexor vs 12.9 months with bortezomib/dexamethasone alone.

As of the data cutoff date of February 18, 2020, the median OS had not yet been reached in the SVd arm vs 25.0 months in the Vd arm.

Rates of any-grade peripheral neuropathy were 32.3% for SVd and 47.1% for Vd (P = .0010). Grade 2 or higher peripheral neuropathy was also reported in 21.0% of patients in the SVd arm vs 34.3% in the Vd arm (P = .0013).

Other safety showed that the most common treatment-emergent adverse effects (AEs) were cytopenias, as well as gastrointestinal and constitutional symptoms, and findings were consistent with previously reported data from other selinexor studies. Most AEs were manageable with dose modifications and/or standard supportive care.

The most common non-hematologic any-grade treatment-related AEs in the selinexor arm included nausea (50%), fatigue (42%), decreased appetite (35%), and diarrhea (32%) and were mostly grade 1 and 2 events. The most common grade 3/4 treatment-related AEs were thrombocytopenia (39%), anemia (16%), and fatigue (13%).

“We are pleased by the MHRA's decision to expand the indication for [selinexor] in Great Britain, bringing this important medicine to more people living with myeloma who may benefit,” Elcin Barker Ergun, chief executive officer of Menarini, said in a news release. “We look forward to delivering [selinexor] to patients and physicians in Great Britain as quickly as possible.”

References

1. Karyopharm and Menarini Group receive full marketing authorization from the UK Medicines & Healthcare Products Regulatory Agency for Nexpovio (selinexor) in combination with bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy. News release. Karyopharm Therapeutics. February 21, 2023. Accessed February 21, 2023. https://investors.karyopharm.com/2023-02-21
2. Grosicki S, Simonova M, Spicka I, et al. Once-per-week selinexor, bortezomib, and dexamethasone versus twice-per-week bortezomib and dexamethasone in patients with multiple myeloma (BOSTON): a randomised, open-label, phase 3 trial. Lancet. 2020;396(10262):1563-1573. doi:10.1016/S0140-6736(20)32292-3
3. Karyopharm announces FDA approval of Xpovio (selinexor) as a treatment for patients with multiple myeloma after at least one prior therapy. News release. Karyopharm Therapeutics, Inc. December 18, 2020. Accessed February 21, 2023. https://investors.karyopharm.com/2020-12-18
4. Bortezomib, selinexor, and dexamethasone in patients with multiple myeloma (BOSTON). ClinicalTrials.gov. Updated January 26, 2023. Accessed February 21, 2023. https://clinicaltrials.gov/ct2/show/NCT03110562
5. Karyopharm announces publication of XPOVIO® (selinexor) phase 3 BOSTON study results in The Lancet. News release. Karyopharm Therapeutics. November 12, 2020. Accessed February 21, 2023. https://investors.karyopharm.com/2020-11-12