Once-weekly selinexor, bortezomib and dexamethasone improved outcomes compared with twice-weekly bortezomib and dexamethasone for pretreated multiple myeloma, according to results presented during the ASCO20 Virtual Scientific Program.
Findings from the randomized phase 3 BOSTON study showed prolonged PFS and a higher objective response rate in the experimental group.
Twice-weekly bortezomib (Velcade, Takeda) is effective as part of combination therapy; however, approximately 50% to 60% of patients develop peripheral neuropathy, limiting the ability to use it for prolonged periods.
Selinexor (Xpovio, Karyopharm Therapeutics) is a first-in-class, oral selective inhibitor of nuclear export compound. The drug binds with and inhibits the nuclear export protein XPO1, leading to the accumulation of tumor suppressor proteins in the cell nucleus.
The agent is approved in the United States for treatment of adults with relapsed or refractory multiple myeloma who received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents and an anti-CD38 monoclonal antibody.
A phase 1b/phase 2 study that evaluated the addition of once-weekly selinexor to bortezomib and dexamethasone showed the combination was well-tolerated and exhibited anti-myeloma activity among patients with proteasome inhibitor-sensitive and -refractory disease.
Meletios A. Dimopoulos, MD, professor in and chairman of the department of clinical therapeutics at National and Kapodistrian University of Athens School of Medicine in Greece, and colleagues conducted the open-label, multicenter BOSTON study to assess whether once-weekly selinexor, bortezomib and dexamethasone improved PFS and ORR while reducing peripheral neuropathy compared with twice-weekly bortezomib and dexamethasone for patients who received one to three prior anti-myeloma regimens.
The analysis included 402 patients (median age, 67 years; range, 38-90; 59.6% aged older than 65 years; 57.1% men). The majority (81.5%) had Revised International Staging System (R-ISS) stage I or stage II disease.
Researchers randomly assigned patients to one of two regimens.
The 195 patients in the experimental group received once-weekly oral selinexor dosed at 100 mg, once-weekly bortezomib administered subcutaneously at a dose of 1.3 mg/m2, and low-dose dexamethasone (40 mg weekly).
The 207 patients in the control group received a standard regimen of twice-weekly bortezomib plus low-dose dexamethasone.
Treatment groups were well-balanced with regard to baseline characteristics.
Study protocol allowed for patients in the control group with confirmed disease progression to cross over to the experimental regimen, or to receive selinexor and dexamethasone alone if they were intolerant to bortezomib.
PFS served as the primary endpoint. Secondary endpoints included ORR, OS, and peripheral neuropathy rates and outcomes.
Investigators stratified randomization by prior treatment with proteasome inhibitors, number of anti-myeloma regimens (1 vs. 2 or more) and R-ISS stage (stage III vs. stage I or stage II).
Researchers reported significantly improved PFS (median, 13.93 months vs. 9.46 months; HR = 0.7; P = .0066) and a significantly higher ORR (76.4% vs. 62.3%; P = .0012) among patients assigned once-weekly selinexor, bortezomib and dexamethasone. Median OS had not been reached in the experimental group and was 25 months among patients assigned twice-weekly bortezomib and dexamethasone, although the difference did not reach statistical significance.
A higher percentage of patients assigned the once-weekly regimen experienced grade 3 or higher thrombocytopenia (35.9% vs 15.2%), fatigue (11.3% vs 0.5%) and nausea (7.7% vs 0%).
However, researchers reported clinically important differences on the motor, autonomic and sensory scales on the EORTC QLQ-CIPN20 questionnaire in the experimental group, and rates of grade 2 or higher peripheral neuropathy were significantly lower among patients assigned that regimen (21% vs. 34.3%; P = .0013).