BOSTON: Weekly Combination Therapy Including Selinexor Improved PFS in Relapsed/Refractory Myeloma

Once weekly combination treatment with selinexor, bortezomib, and dexamethasone (SVd) led to an approximately 4-month improvement in progression-free survival (PFS) compared with bortezomib plus dexamethasone (Vd) in patients with relapsed or refractory multiple myeloma, according to the results of the phase III BOSTON study. Meletios A. Dimopoulos, MD, of National and Kapodistrian University of Athens School of Medicine in Greece, presented the findings as part of the ASCO20 Virtual Scientific Program.

Selinexor is an oral, selective inhibitor of XPO1-mediated nuclear export that, in combination with dexamethasone, induced a partial response or better in 26% of 122 patients with relapsed/refractory myeloma enrolled in the phase Ic/II STORM study (NCT02336815) reported in 2019 in the New England Journal of Medicine.

The BOSTON study randomly assigned 402 patients with 1 to 3 prior therapies to either weekly SVd (n=195) or twice weekly Vd (n=207). Upon disease progression, crossover was permitted to SVd for patients who could continue to tolerate bortezomib, or selinexor and dexamethasone for those with bortezomib intolerance. The primary endpoint was PFS.

Overall rates of peripheral neuropathy were significantly lower with SVd than with Vd (p=0.001). However, patients assigned to SVd experienced high rates of certain grade 3 or higher adverse events, including thrombocytopenia (35.9% vs. 17.2%), fatigue (13.3% vs. 1.0%), and nausea (7.7% vs. 0%).

The selinexor combination significantly prolonged PFS, with a median of 13.9 months compared with 9.5 months for Vd alone (hazard ratio [HR] = 0.70; p=0.0066). PFS benefit was seen across all subgroups, including those with high-risk cytogenetics and those with 17p deletion. The benefit was greatest in patients who had not received a prior proteasome inhibitor.

The overall response rate was also higher in patients assigned to SVd (76.4% vs. 62.3%; p=0.0012). Patients assigned to weekly SVd also had a significantly higher rate of deep responses. In the weekly SVd group, 44.6% of patients achieved a very good partial response or better compared with 32.4% in the Vd arm (p=0.0082). Time to next treatment was also longer with selinexor compared with Vd (16.1 vs. 10.8 months; HR=0.66; p=0.0012).

An interim analysis of overall survival showed a median survival not reached for weekly SVd compared with 25 months for Vd (HR=0.84; 95% CI 0.57-1.23; p=0.19).

“These data indicate that a once weekly regimen of selinexor plus bortezomib and dexamethasone is more active, and more convenient for patients, than twice weekly bortezomib and dexamethasone for patients with relapsed/refractory multiple myeloma,” Dr. Dimopoulos said.


  1. Dimopoulos MA, Delimpasi S, Simonova M, et al. Weekly Selinexor, bortezomib, and dexamethasone (SVd) versus twice weekly bortezomib and dexamethasone (Vd) in patients with multiple myeloma (MM) after one to three prior therapies: Initial results of the phase III BOSTON study. J Clin Oncol. 2020;38(suppl):abstr 8501. Presented as part of the ASCO20 Virtual Scientific Program. May 29-31, 2020.
  2. Chari A, Vogl DT, Gavriatopoulou M. Oral selinexor-dexamethasone for triple-class refractory multiple myeloma. N Engl J Med. 2019 Aug 22;381(8):727-738.