FDA Approves Selinexor Combination Treatment for Certain Patients With Multiple Myeloma

Officials with the FDA have approved selinexor (Xpovio; Karyopharm Therapeutics Inc.) in combination with bortezomib (Velcade; Takeda) and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least 1 prior therapy.

Selinexor is a first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) medicine and was previously approved under the FDA's Accelerated Approval Program for the treatment of adult patients with relapsed or refractory multiple myeloma (R/RMM) who have received at least 4 prior therapies and whose disease is refractory to at least 2 proteasome inhibitors, at least 2 immunomodulatory agents, and an anti-CD38 monoclonal antibody.

According to Sharon Shacham, PhD, MBA, Founder, President and Chief Scientific Officer of Karyopharm, the FDA’s approval of selinexor to achieve expanded reach into the patient population. The drug’s label expansion was supported by the phase 3 BOSTON (NCT03110562) study, Shacham said in a prepared statement.

The BOSTON study evaluated 402 adult patients at more than 150 sites internationally with R/RMM who had received 1 to 3 prior lines of therapy. The study was designed to compare the efficacy, safety and certain health-related quality of life parameters of once-weekly Selinexor in combination with once-weekly bortezomib plus low-dose dexamethasone (SVd) versus twice-weekly bortezomib plus dexamethasone (Vd). The primary endpoint of the study was progression-free survival (PFS) and key secondary endpoints included overall response rate (ORR), rate of peripheral neuropathy, and others. Additionally, the BOSTON study allowed for patients on the Vd control arm to crossover to the SVd arm following objective progression of disease verified by an Independent Review Committee (IRC).

According to Karyopharm, although the study had one of the highest proportions of patients with high-risk cytogenetics (~50%) as compared with other bortezomib-based studies in previously treated multiple myeloma, the median PFS in the SVd arm was 13.9 months compared to 9.5 months in the Vd arm, representing a 4.4 month (47%) increase in median PFS (hazard ratio of 0.70; p=0.0075). The SVd arm also demonstrated a significantly greater ORR compared to the Vd arm (76.4% vs. 62.3%, p=0.0012). Importantly, SVd therapy compared to Vd therapy showed consistent PFS benefit and higher ORR across several important subgroups.

"Patients receiving SVd had approximately 35% fewer clinic visits compared to those receiving the standard, twice-weekly Vd regimen, thus receiving 40% less bortezomib and 25% less dexamethasone as compared with the control arm in the first 24 weeks of therapy. This once-weekly dosing feature helps makes the SVd regimen attractively simple…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," said 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, in a prepared statement.

The most common adverse reactions were cytopenias, along with gastrointestinal and constitutional symptoms and were consistent with those previously reported from other selinexor studies. Most adverse reactions were manageable with dose modifications and/or standard supportive care. The most common nonhematologic adverse reactions were

fatigue (59%),

nausea (50%),

decreased appetite (35%), and diarrhea (32%), and were mostly Grade 1 and 2 events. The most common Grade 3 and 4 adverse reactions were thrombocytopenia (43%), lymphopenia (38%),

fatigue (28%) and anemia (17%).

According to Michael G. Kauffman, MD, PhD, Chief Executive Officer of Karyopharm, the company plans to immediately launch selinexor in this earlier-line indication.

In addition to multiple myeloma, selinexor 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.

REFERENCE

Karyopharm Announces FDA Approval of XPOVIO® (Selinexor) as a Treatment for Patients with Multiple Myeloma After At Least One Prior Therapy [news release]. Newton, MA; December 18, 2020: Karyopharm Therapeutics Inc. Accessed December 18, 2020. https://investors.karyopharm.com/2020-12-18-Karyopharm-Announces-FDA-Approval-of-XPOVIO-R-Selinexor-as-a-Treatment-for-Patients-with-Multiple-Myeloma-After-At-Least-One-Prior-Therapy