The combination of once-weekly selinexor with bortezomib and dexamethasone (SVd) demonstrated a 30% reduction in the risk of disease progression or death, compared with bortezomib-dexamethasone (Vd) alone, in patients with relapsed/refractory multiple myeloma (MM), according to data from the randomized, phase III BOSTON trial. These results, which were published in The Lancet, supported the FDA’s approval of SVd for the treatment of adults with MM who have received at least one prior therapy.
“Notably, the improved efficacy was achieved during the first 24 weeks of treatment, when patients in the selinexor, bortezomib, and dexamethasone group were receiving 40% less bortezomib and 25% less dexamethasone than patients in the bortezomib and dexamethasone group,” the authors, led by Sebastian Grosicki, MD, PhD, from the Medical University of Silesia in Katowice, Poland, wrote.
The open-label, international BOSTON trial enrolled adults with MM who had previously received one to three lines of therapy, including proteasome inhibitors. A total of 402 participants were randomized 1:1 to receive either:
- SVd: selinexor 100 mg once per week plus bortezomib 1.3 mg/m² once per week and dexamethasone 20 mg twice per week (n=195)
- Vd: bortezomib 1.3 mg/m² twice per week for the first 24 weeks and once per week thereafter and dexamethasone 20 mg 4 times per week for the first 24 weeks and twice per week thereafter (n=207)
Median ages in the SVd and Vd groups were 66 and 67 years, respectively, and about half of participants in each treatment group had at least one high-risk cytogenetic abnormality such as del17p or t(14;16). The median number of previous regimens was two, and the most common therapy received immediately prior to study entry was bortezomib (69% in SVd and 70% in Vd). The primary reason for treatment discontinuation was disease progression.
After a median follow-up period of 13.2 months in the SVd group and 16.5 months in the Vd group, median progression-free survival (PFS) was significantly longer with selinexor treatment: 13.93 months versus 9.46 months (hazard ratio [HR] = 0.70; 95% CI 0.53-0.93; p=0.0075). The investigators added that the PFS benefit with SVd was consistent across subgroups, including patients age 65 or older (HR=0.55), those with high-risk cytogenetic abnormalities (HR=0.67), and those previously treated with lenalidomide (HR=0.63).
Response rates also were greater in the selinexor group than the Vd group: 74.6% versus 62.3% (odds ratio = 1.96; 95% CI 1.3-3.1; p=0·0012). More patients in the SVd group experienced at least a very good partial response, however, the researchers reported that the proportion of patients who had stable disease or progressive disease as their best response was lower in the selinexor group (TABLE).
Median duration of response was significantly longer with SVd (20.3 months vs. 12.9 months; HR=0.81; 95% CI 0.56-1.17; p=0.1364). The authors also reported that treatment with selinexor appeared to prolong the time to next anti-myeloma treatment (16.1 months vs. 10.8 months; HR=0.66; 95% CI 0.50-0.86]; p=0.0012).
Nearly one-quarter of patients in the SVd group (n=47) died during follow-up, compared with nearly one-third of patients in the Vd group (n=62). Median overall survival was not reached in the selinexor group and was 25 months in the Vd group (HR=0.84; 95% CI 0.57-1.23]; p=0.1852).
The improvements in survival and response rates with selinexor were accompanied by higher rates of adverse events (AEs), the most common of which were:
- thrombocytopenia: 60% with SVd and 27% with Vd
- nausea: 50% and 10%
- fatigue: 42% and 18%
- anemia: 36% and 23%
However, the incidence of peripheral neuropathy was significantly lower in the selinexor group, both any grade events (32% vs. 47%) and grade 3-4 events (4.6% vs. 8.8%). “The lower frequency and severity of peripheral neuropathy could substantially improve patient quality of life,” the researchers noted.
Selinexor treatment was also associated with a higher rate of treatment discontinuation due to treatment-emergent AEs (21% vs. 16%), mostly due to peripheral neuropathy.
Although the study’s findings are limited by its open-label design, which the authors wrote “was considered to be suitable given the different requirements for once-per-week versus twice-per-week subcutaneous bortezomib in the two groups of the study,” they concluded that these findings support SVd as a “potent and convenient” treatment option for patients with previously treated MM.
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.