As reported in The Lancet by Grosicki et al, the phase III BOSTON trial has shown significantly prolonged progression-free survival with once-weekly selinexor plus bortezomib/dexamethasone vs twice-weekly bortezomib/dexamethasone in previously treated patients with multiple myeloma.

Study Details

The open-label trial included 402 patients from sites in 21 countries who had previously received one to three lines of therapy. Patients were randomly assigned to receive oral selinexor at 100 mg once per week, subcutaneous bortezomib at 1.3 mg/m² once per week, and oral dexamethasone at 20 mg twice per week (selinexor group; n = 195) or bortezomib at 1.3 mg/m² twice per week for the first 24 weeks and once per week thereafter and dexamethasone at 20 mg four times per week for the first 24 weeks and twice per week thereafter (control group; n = 207). The first dose of both study regimens was given between June 2017 and February 2019. Crossover to selinexor plus bortezomib/dexamethasone was permitted upon disease progression in the control group. Overall, 69% of patients had previously received bortezomib. The primary endpoint was progression-free survival as determined by independent review committee in the intention-to-treat population.

Progression-Free Survival

Median follow-up for progression-free survival was 13.2 months in the selinexor group and 16.5 months in the control group. Median progression-free survival was 13.93 months (95% confidence interval [CI] = 11.73 months–not evaluable) in the selinexor group vs 9.46 months (95% CI = 8.11–10.78 months) in the control group (hazard ratio [HR] = 0.70, 95% CI = 0.53–0.93, P = .0075).

Objective response was observed in 76.4% vs 62.3% of patients (odds ratio [OR] = 1.96, 95% CI = 1.3–3.1, P = .0012), with very good partial response or better occurring in 44.6% vs 32.4% (OR = 1.66, P = .0082). Median duration of response was 20.3 months (95% CI = 12.5 months–not evaluable) vs 12.9 months (95% CI = 9.3–15.8 months; HR = 0.81, P = .1364).

“A once-per-week regimen of selinexor, bortezomib, and dexamethasone is a novel, effective, and convenient treatment option for patients with multiple myeloma who have received one to three previous lines of therapy.”

— Grosicki et al

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Overall, 63 patients in the control group (30%) crossed over to selinexor plus bortezomib/dexamethasone treatment at disease progression. At time of data cutoff, after median follow-up for overall survival of 17.3 months vs 17.5 months, death had occurred in 47 patients (24%) in the selinexor group vs 62 patients (30%) in the control group. Estimated median overall survival was not reached in the selinexor group vs 25 months (95% CI = 23.5 months–not evaluable) in the control group (HR = 0.84, 95% CI =0.57–1.23, P = .1852).

Adverse Events

The most frequent grade 3 or 4 adverse events—all in the selinexor group—were thrombocytopenia (39% vs 17%), anemia (16% vs 10%), fatigue (13% vs 1%), and pneumonia (11% vs 11%). Peripheral neuropathy of grade ≥ 2 occurred in 21% vs 34% of patients (odds ratio = 0.50, P = .0013). Serious adverse events occurred in 52% vs 38% of patients, with the most common in both groups being pneumonia (12% in each group). Adverse events led to treatment discontinuation in 21% vs 16% of patients. Death due to adverse events occurred in 12 patients (6%) in the selinexor group, with 4 deaths considered related to treatment, and in 11 patients (5%) in the control group, with 1 considered related to treatment.

The investigators concluded, “A once-per-week regimen of selinexor, bortezomib, and dexamethasone is a novel, effective, and convenient treatment option for patients with multiple myeloma who have received one to three previous lines of therapy.”

Sebastian Grosicki, MD, of the Medical University of Silesia, Katowice, Poland, is the corresponding author for The Lancet article.

Disclosure: The study was funded by Karyopharm Therapeutics. For full disclosures of the study authors, visit thelancet.com.