Selinexor Receives Approval in South Korea for Multiple Myeloma

The South Korean Ministry of Food and Drug Safety has approved a supplemental new drug application (sBLA) for selinexor (Xpovio) in combination with bortezomib (Velcade) and dexamethasone (SVd) for the treatment of adult patients with multiple myeloma who have received at least 1 prior line of therapy.¹

The announcement was made on the heels of 2 prior approvals in South Korea, listing selinexor for use in combination with dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma and as monotherapy for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma.

On July 24, 2024, selinexor was added to the reimbursement drug list in South Korea, becoming the first XPO1 inhibitor to receive approval for public insurance coverage in the country. The agent is also included in national health insurance or reimbursement schemes in Australia and Singapore. 

In December 2020 the FDA approved SVd for the treatment of patients with multiple myeloma who have received at least 1 prior line of therapy. The approval was based on data from the phase 3 BOSTON trial (NCT03110562) which compared the regimen with bortezomib and dexamethasone (Vd) alone in patients who had received at least 1 but no more than 3 prior lines of therapy.²

At the time of approval, the study had demonstrated a statistically significant improvement in the primary end point of progression-free survival (PFS), showcasing an estimated PFS of 13.9 months (95% CI, 11.7-not estimable) with the investigational regimen vs 9.5 months (95% CI, 7.6-10.8) with Vd alone (HR, 0.70; 95% CI, 0.53-0.93; one-sided P = .0075). Additionally, the overall response rates with SVd and Vd were 76.4% (95% CI, 69.8%-82.2%) and 62.3% (95% CI, 55.3%-68.9%), respectively (one-sided P =.0012).³ With median follow-up of 17.4 months the median overall survival (OS) was not reached (NR) with SVd vs 25.0 months with Vd alone (HR, 0.84; 95% CI, 0.57-1.23; P =.19).⁴

Findings from an extended, post-hoc follow-up analysis recently published in the European Journal of Hematology demonstrated that at a median follow-up of over 28 months SVd maintained clinically meaningful improvements in PFS vs Vd alone across all subgroups. The median PFS in patients with lenalidomide (Revlimid)-refractory disease was 10.2 months with SVd vs 7.1 months with Vd (HR, 0.52; 95% CI, 0.31-0.88; P =.006). Patients who had not received a prior proteasome inhibitor had a median PFS of 29.5 months with SVd vs 9.7 months with Vd (HR, 0.29; 95% CI, 0.14-0.63; P <.001). Among those who were bortezomib-naïve the median PFS with SVd and Vd were 29.5 months and 9.7 months, respectively (HR, 0.35; 95% CI, 0.18-0.68; P =.001). Notably, patients who had received 1 prior line of therapy had an approximate doubling in median PFS with SVd, at 21.0 months vs 10.7 months with Vd alone (HR, 0.62; 95% CI, 0.41-0.95; P =.014).⁵

Patients with lenalidomide-refractory disease also experienced longer median OS with SVd, at 26.7 months vs 18.6 months with Vd alone (HR, 0.53; 95% CI, 0.30-0.95; P =.015). Patients who were proteasome inhibitor–naive and bortezomib-naive had a median OS that was NR in either arm (HR, 0.54; 95% CI, 0.25-1.20; P=.062 and HR, 0.56; 95% CI, 0.27-1.15; P =.055, respectively). Patients who had received 1 prior line of therapy experienced a median OS that was NR with SVd vs 32.8 months with Vd (HR, 0.91; 95% CI, 0.57-1.45; P =.344).⁵

Antengene, codeveloper of selinexor, has also submitted a new drug application for the agent in Indonesia, with approval expected in the second half of 2024.¹

References

1. Antengene announces Xpovio (selinexor) approved for its third indication in South Korea, bringing fresh hope to patients with MM in the country. News release. Antengene Corporation Limited. October 18, 2024. Accessed October 18, 2024. https://www.antengene.com/newsinfo/411
2. FDA approves selinexor for refractory or relapsed multiple myeloma. FDA. December 18, 2020. Accessed October 18, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-selinexor-refractory-or-relapsed-multiple-myeloma#:~:text=On%20December%2018%2C%202020%2C%20the,at%20least%20one%20prior%20therapy
3. Xpovio. Prescribing information. Karyopharm Therapeutics; 2020. Accessed October 18, 2024. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/212306s005lbl.pdf
4. Dimopoulos MA, Delimpasi S, Simonova M, et al. Weekly selinexor, bortezomib, and dexamethasone (SVd) versus twice weekly bortezomib and dexamethasone (Vd) in patients with multiple myeloma (MM) after one to three prior therapies: initial results of the phase III BOSTON study. J Clin Oncol. 2020;38(suppl 5):8501. doi:10.1200/JCO.2020.38.15_suppl.8501
5. Mateos MV, Engelhardt M, Leleu X, et al. Impact of prior treatment on selinexor, bortezomib, dexamethasone outcomes in patients with relapsed/refractory multiple myeloma: extended follow-up subgroup analysis of the BOSTON trial. Eur J Haematol. 2024;113(2):242-252. doi:10.1111/ejh.14223