When added to bortezomib and dexamethasone in patients with multiple myeloma, selinexor significantly improved progression-free survival and response rates, with a lower incidence of peripheral neuropathy, compared with bortezomib/dexamethasone alone, according to results from the global phase III BOSTON trial.1 Selinexor, a first-in-class oral inhibitor of XPO1-mediated nuclear export, reactivates tumor suppressor proteins. The drug was first approved in 2019 by the U.S. Food and Drug Administration in combination with dexamethasone for heavily pretreated patients whose disease was refractory to two or more proteasome inhibitors, two immunomodulatory agents, and an anti-CD38 monoclonal antibody.
Meletios A. Dimopoulos, MD
Meletios A. Dimopoulos, MD, of the National and Kapodistrian University of Athens School of Medicine in Greece presented the results at the ASCO20 Virtual Scientific Program. BOSTON is the first phase III study to evaluate the benefit of this regimen for relapsed/refractory multiple myeloma.
In the BOSTON study, 402 previously treated patients received bortezomib at a dose of 1.3 mg/m2 plus dexamethasone at 20 mg twice weekly, or the same plus selinexor 100 mg once weekly. In the selinexor arm, the bortezomib dose was reduced by 40% and the dose of dexamethasone was reduced by 25% at 24 weeks. Patients who experienced disease progression on bortezomib/dexamethasone could cross over to the triplet or to selinexor plus dexamethasone.
Triplet Regimen Benefits All Subgroups
Selinexor/bortezomib/dexamethasone significantly prolonged median progression-free survival compared with the doublet: 13.93 months vs 9.46 months (hazard ratio [HR] = 0.70; P = .0075). This was true for all subgroups, including patients with 17p deletions and those previously treated with lenalidomide.
“As lenalidomide is often used in the front-line setting and with daratumumab, having an IMiD [immunomodulatory drug]-free option in the relapsed setting with a novel mode of action is an important finding from the BOSTON trial,” said Dr. Dimopoulos.
Response rates were also significantly higher with the triplet (76.4% vs 62.3%; P = .0012). Median overall survival was not reached in the selinexor group and was 25 months in the doublet group (hazard ratio = 0.84; P = .19). Significantly longer duration of response and time to next therapy were achieved with selinexor and peripheral neuropathy grade ≥ 2 was less (21% vs 34%; P = .0013). The triplet was, however, associated with more thrombocytopenia, fatigue, nausea, and treatment-related discontinuations.
“Overall, these data indicate that the once-weekly regimen of selinexor plus bortezomib and dexamethasone could be a new standard of care and, by requiring 40% fewer clinic visits, a most convenient triplet therapy,” he said.
DISCLOSURE: Dr. Dimopoulos has received honoraria from, or has consulted or advised for, Amgen, Bristol-Myers Squibb, Celgene, Janssen-Cilaq, and Takeda.
1. Dimopoulos MA, Delimpasi S, Simonova M, et al. Initial results of the phase III BOSTON study. ASCO20 Virtual Scientific Program. Abstract 8501.