Once weekly selinexor, bortezomib, and dexamethasone induces better responses than bortezomib and dexamethasone in previously treated patients with multiple myeloma, according to research published in the Lancet.
Relapsed or refractory disease remains a challenge in treating multiple myeloma, creating a need for novel combination therapies. Selinexor has shown promise in previous trials when combined with bortezomib and dexamethasone in patients not refractory to proteasome inhibitors.
The BOSTON trial is a phase 3, multicenter trial comparing triplet therapy with selinexor to doublet therapy for patients with previously treated myeloma. Patients were randomized to groups to either receive once weekly selinexor, bortezomib and dexamethasone (n = 195) or bortezomib and dexamethasone (n = 207). Patients had received at least 1, but no more than 3, previous therapies for multiple myeloma.
The triplet combination reduced the risk of progression or death by 30% and improved outcomes over doublet therapy. The survival benefit was seen across subgroups, including patients older than 65 years and patients with cytogenetic abnormalities.
The overall response rate (ORR) in the triplet therapy group was 76.4% vs 62.3% in the doublet therapy group (P =.0012). Median progression free survival (PFS) was 13.93 months with triplet therapy and 9.46 months with doublet (P =.0075). The triplet therapy group had slightly more patients experiencing a very good partial response or partial response, and fewer patients experiencing stable or progressive disease as their best response.
Triplet therapy had higher rates of thrombocytopenia, anemia, pneumonia and fatigue, which were the most common adverse events in both groups. Grade 2 or above peripheral neuropathy was less frequent in the selinexor group. The study authors noted that peripheral neuropathy is the most common dose-limiting toxicity associated with bortezomib.
The triplet therapy used in the study reduced the amount of bortezomib and dexamethasone patients received, which lowered the frequency and severity of peripheral neuropathy. Once weekly triplet therapy is a simpler therapy than other triplet therapies that could improve quality of life.
Disclosures: Some authors have declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.
Grosicki S, Simonova M, Spicka I, et al. Once-per-week selinexor, bortezomib, and dexamethasone versus twice-per-week bortezomib and dexamethasone in patients with multiple myeloma (BOSTON): a randomised, open-label, phase 3 trial. Lancet. 2020;396(10262):1563-1573. doi:10.1016/S0140-6736(20)32292-3