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 Ib/II study.
The BOSTON trial is an ongoing phase III, randomized study of once-weekly SVd versus twice-weekly Vd after one to three prior anti–MM regimens. The primary endpoint is PFS, and key secondary endpoints include ORR, overall survival (OS), and outcomes related to peripheral neuropathy, 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 selinexor to Vd indicated an early and persistent PFS benefit. Patients in the SVd arm had substantially prolonged PFS compared with those in the Vd arm (median, 13.93 vs. 9.46 months; HR, 0.70; P = .0075). Dr Dimopoulos emphasized that in the subgroup analysis, the PFS benefit was also observed in patients previously exposed to lenalidomide. He noted, “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.”
The presentation at the ASCO 2020 meeting revealed that the ORR was also considerably greater in the SVd arm compared with the Vd arm (76.4% vs. 62.3%; P = .0012). The ORR benefit was also observed across all subgroups, including patients aged 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 peripheral neuropathy was significantly lower with SVd than with Vd (32.3% vs. 47.1%; P = .0013).
The most frequent treatment-related adverse events (grade ≥3) for SVd versus 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 comparable 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%).
Dr. Dimopoulos revealed, “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].
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