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Weekly Selinexor Added to Bortezomib and Dexamethasone Improves Outcomes in MM
Once weekly selinexor, bortezomib, and dexamethasone (SVd) significantly improved progression-free survival (PFS) and overall response rates (ORR) compared to standard twice weekly bortezomib and dexamethasone (Vd) for multiple myeloma (MM), according to results from the BOSTON study presented at the virtual 2020 ASCO Annual Meeting.
“In a phase 1b/2 study, the combination of once weekly… [SVd] was well tolerated with anti-MM activity in patients with PI-sensitive and PI-refractory disease. While twice weekly bortezomib in combination therapy is efficacious, prolonged use is limited due to peripheral neuropathy” explained Meletios A. Dimopoulos, MD, National and Kapodistrian University of Athens School of Medicine, Greece, during his presentation.
The randomized, phase 3 BOSTON study evaluated once weekly SVd compared with twice weekly Vd for patients who received 1-3 prior anti-MM therapies. Randomization was stratified by treatment with prior PR therapies, number of prior anti-MM regimens (1 vs >1), and Revised International Staging System (R-ISS; Stage III vs I or II).
The primary end point of the study is PFS. Secondary end points include ORR, overall survival (OS), and rate of peripheral neuropathy (grade ≥2).
Patients with disease progression on Vd were able to cross over to either SVd (for those able to tolerate continued bortezomib) or selinexor plus dexamethasone (for those with bortezomib intolerance).
A total of 402 patients were enrolled and randomized to SVd (n = 195) or Vd (n = 207). Baseline characteristics were well-balanced across the treatment arms.
Median PFS with SVd was 13.93 months compared with 9.46 months with Vd (hazard ratio [HR}, 0.70; P = .0066). In the SVd arm, ORR was 76.4% compared with 62.3% with Vd (P = .0012). Median OS was not reached versus 25 months, respectively (P = .28).
The most common treatment-related adverse events (grade ≥3) were thrombocytopenia (35.9% with SVd vs 15.2% with Vd), fatigue (11.3% vs 0.5%, respectively) and nausea (7.7% vs 0%, respectively). Rates of peripheral neuropathy (grade ≥2) were significantly lower with SVd compared with Vd (21% vs 34.3%; P = .0013).
“Overall, this data indicates that a once weekly regimen of selinexor plus bortezomib and dexamethasone could be a new standard of care and most convenient therapy for patients with MM,” Dr Dimopoulos concluded.—Janelle Bradley
Dimopoulos M, 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: the 2020 ASCO Annual Meeting; May 29-31, 2020. Abstract 8501.
