Novel Triple Therapy With First-in-Class Selinexor Improves Outcomes in Multiple Myeloma

The phase 3 BOSTON trial evaluated selinexor, bortezomib, and dexamethasone (SVd) vs bortezomib and dexamethasone (Vd) in patients with multiple myeloma (MM) and met its primary endpoint; finding that weekly SVd significantly improved progression-free survival (PFS) and overall response rate (ORR) compared to twice-weekly Vd.

The initial results of BOSTON (ClinicalTrials.gov Identifier: NCT03110562) were presented by Meletios Dimopoulos, MD, of the University of Athens in Greece, during the ASCO20 Virtual Scientific Program.

Selinexor is a first-in-class oral, selective inhibitor of exportin-1, which is upregulated in MM. Previously, once-weekly SVd was well tolerated and exhibited anti-MM activity in patients with relapsed/refractory MM in a phase 1b/2 study.

The BOSTON trial is an ongoing, phase 3, randomized study of once-weekly SVd vs twice-weekly Vd after 1 to 3 prior anti-MM regimens. The primary endpoint is PFS, and key secondary endpoints include ORR, overall survival (OS) and outcomes related to peripheral neuropathy (PN), which limits prolonged use of the twice-weekly Vd regimen in many patients with MM.

In total, 402 patients, with a median age of 67 years (range, 38-90 years), were enrolled in the study (195 received SVd and 207 received Vd; 57.1% were men). Baseline patient and disease characteristics were well balanced across the treatment arms.

Adding S to Vd showed an early and sustained PFS benefit. Patients in the SVd arm had significantly prolonged PFS compared to those in the Vd arm (median, 13.93 vs 9.46 months; HR, 0.70; P =.0075). Dr Dimopoulos highlighted that in the subgroup analysis the PFS benefit was also seen in patients previously exposed to lenalidomide.

“As lenalidomide is often used in the front-line setting and with daratumumab having an IMiD-free option in the relapse setting with a novel mode of action is an important finding from the BOSTON trial,” he explained.

The ORR was also significantly higher in the SVd arm compared with the Vd arm (76.4% vs 62.3%, P =.0012). This benefit in ORR was also observed across all subgroups, including patients 65 years and older and high-risk cytogenetics, among others. Median OS was 25 months with Vd and has not yet been reached with SVd. The overall rate of PN was significantly lower with SVd than with Vd (32.3% vs 47.1%; P =.0013).

The most frequent treatment-related AEs (grade ≥3) for SVd vs Vd were thrombocytopenia (39.5% vs 17.2%, respectively), fatigue (13.3% vs 1.0%, respectively), and nausea (7.7% vs 0%, respectively).

Treatment discontinuation was similar in both arms (81% SVd vs 82% Vd). Disease progression was the most common reason for discontinuation (34% in the SVd arm vs 52% in the Vd arm). At 17.4 months follow-up, more deaths had occurred in the Vd arm (30%) than in the SVd arm (24%).

“Overall these data indicate that a once-weekly regimen of [SVd] could be a new standard of care and a most convenient triplex therapy [in patients with multiple myeloma],” concluded Dr Dimopoulos.

Disclosures: Some authors have declared affiliations with the pharmaceutical industry. Please refer to the original study for a full list of disclosures.

Reference

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. Presented at: ASCO20 Virtual Scientific Program. J Clin Oncol. 2020;38(suppl):abstr 7031.