The triplet combination of selinexor, bortezomib, and dexamethasone demonstrated an improved median progression-free survival rate over the standard regimen of bortezomib and dexamethasone in treating patients with multiple myeloma in the BOSTON trial
The triplet combination of selinexor (Xpovio), bortezomib (Velcade), and dexamethasone (SVd) demonstrated an improved median progression-free survival (PFS) rate over the standard regimen of bortezomib and dexamethasone (Vd) in treating patients with multiple myeloma in the BOSTON trial (NCT03110562), announced Karyopharm Therapeutics, Inc, in a news release.1Investigators reported that patients in the SVd arm had a median PFS of 13.93 months compared with 9.46 months in patients in the Vd arm, which represented a 4.47-month improvement (47%; HR, 0.70;P= .0066).
Efficacy, safety, and health-related quality of life parameters were measured in the phase III trial involving 402 patients comparing once-weekly SVd versus twice-weekly SVd in patients with relapsed or refractory multiple myeloma who had previously received 1 to 3 prior lines of therapy. PFS was the primary end point and overall response was the secondary end point. Patients in the Vd arm were allowed to crossover following quantitative disease progression. No new safety signals on the SVd regimen were observed and there was no imbalance in deaths observed between the 2 arms of the study.
Patients on the SVd arm received oral selinexor once a week (100 mg), subcutaneous bortezomib (1.3 mg/m2) once a week, and dexamethasone (40 mg) once a week. Patients on the Vd arm received bortezomib twice a week and dexamethasone, given on a standard dose on the recommended schedule.
“We are thrilled to report these highly significant top-line results from the BOSTON study, the first randomized phase III trial to demonstrate clinically and statistically significant activity of once-weekly Xpovio in combination with a current standard of care treatment in patients with myeloma after 1 to 3 prior therapies,” said Sharon Shacham, PhD, MBA, president and chief scientific officer of Karyopharm, in a statement.
“In the study, patients on the SVd regimen lived 47% longer without their disease worsening, which we believe represents an important improvement in the treatment of patients with relapsed or refractory multiple myeloma,” continued Shacham.
The company plans to submit the full data set for presentation at upcoming medical conferences. In addition, a supplemental New Drug Application will be submitted to the FDA for an expanded indication for selinexor in the second-line treatment for patients with relapsed or refractory multiple myeloma in the second quarter of 2020.
“If approved, the SVd regimen would be the first and only FDA-approved combination drug regimen that includes once-weekly Velcade therapy for relapsed myeloma,” said Shacham.
To be included in BOSTON, patients had to have histologically confirmed multiple myeloma per the International Myeloma Working Group, received at least 1 prior antimultiple myeloma regimen with no more than 3 prior anti–multiple myeloma regimens, and an ECOG status of 0 to 2. Patients were ineligible if they had a prior malignancy requiring treatment, uncontrolled active infection, documented systemic light chain amyloidosis, or multiple myeloma involving the central nervous system.
Selinexor was approved by the FDA in July 2019 in combination with dexamethasone for the treatment of adult patients with relapsed/refractory multiple myeloma 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. The agent is being evaluated in several other mid-and later-phase clinical trials across multiple cancer indications, including liposarcoma (SEAL trial) and endometrial cancer (SIENDO trial), among others.
Karyopharm announces phase 3 BOSTON study meets primary endpoint with significant increase in progression-free survival in patients with multiple myeloma following one to three prior lines of therapy [news release]. March 2, 2020. https://bit.ly/3coR6q6. Accessed March 2, 2020.