A once-per-week selinexor, bortezomib, plus dexamethasone treatment strategy appeared effective and convenient as treatment of patients with multiple myeloma who received at least 1 to 3 prior lines of therapy.
A once-per-week selinexor (Xpovio), bortezomib (Velcade), plus dexamethasone treatment strategy appeared effective and convenient as treatment of patients with multiple myeloma who received at least 1 to 3 prior lines of therapy, according to findings from the phase 3, randomized, open-label BOSTON trial.
The study was conducted across 123 sites in 21 countries, and patients were randomized 1:1 to 1 of 2 arms; patients received selinexor 100 mg once per week, bortezomib 1.3 mg/m2 once per week, and dexamethasone 20 mg twice per week, or in the second arm, patients were treated with bortezomib 1.3 mg/m2twice 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.
The primary end point of the study is progression-free survival (PFS), and secondary end points included objective response rate (ORR), overall survival (OS), and duration of response (DOR), as well as PFS and ORR in patients who crossed over from the control arm, PFS on subsequent line of therapy, time to next anti-multiple myeloma treatment, time to response, incidence of grade 2 or higher peripheral neuropathy events, and patient-reported peripheral neuropathy. Safety and tolerability were also reviewed as additional secondary end points.
The median age of patients in the experimental arm was 66 years (range, 59-72) compared with 67 years (range, 61-74) in the control arm, and the majority of patients were male in both arms (59% and 56%, respectively). Among patients randomized to the triplet arm (n = 195), 54% had an ECOG performance status of 1, 35% 0, and 10% 2, compared with 55%, 37%, and 8% in the control arm, which included 207 patients total. Most patients (51%) had received 1 prior line of therapy in the experimental arm versus 48% in the control, while 33% and 31% had 2 prior lines, and 16% and 21% had 3 prior lines, respectively.
Overall, the PFS was significantly longer with the triplet regimen compared with bortezomib and dexamethasone alone. The median PFS was 13.93 months (95% CI, 11.73-not evaluable [NE]) in the experimental arm versus 9.46 months (95% CI, 8.11-10.78) in the control arm (HR, 0.70; 95% CI, 0.53-0.93; P=.0075).
The ORR was significantly higher with the once-per-week regimen at 76.4% (95% CI, 69.8-82.2) compared with 62.3% (95% CI, 55.3-68.9) in the control arm (OR, 1.96; 95% CI, 1.3-3.1; P =.0012). In the triplet arm, the proportion of patients with a very good partial response or was 44.6% (95% CI, 37.5-51.9) compared with 32.4% (95% CI, 26.0-39.2) in the bortezomib plus dexamethasone arm (OR, 1.66; 95% CI, 1.1-2.5; P =.0082). The proportion of patients with stable disease or progressive disease as their best response was also lower in the triplet arm at 13.3% (95% CI, 8.9-18.9) compared with 24.2% in the control arm (95% CI, 18.5-30.6).
The median time to first response of a partial response or better was 1.1 months (interquartile range [IQR], 0.8-1.6) in the triplet arm versus 1.4 months (IQR, 0.8-1.6) in the control arm. The median duration of response was longer with the once-per-week regimen at 20.3 months (95% CI, 12.5-NE) compared with 12.9 months (95% CI, 9.3-15.8) in the control (HR, 0.81; 95% CI, 0.56-1.17; P =.1364). The median time to next anti-myeloma therapy was longer in the triplet arm as well at 10.8 months (95% CI, 9.8-13.4) versus 0.66 (95% CI, 0.50-0.86) in the control (P =.0012).
Overall, 47 patients (24%) died in the experimental arm compared with 62 (30%) in the control arm. The median OS was not reached after a median follow-up of 17.3 months in the triplet arm (IQR, 12.9-20.3) versus 25 months (95% CI, 23.5-NE) after 17.5 months follow-up in the experimental arm (HR, 0.84; 95% CI, 0.57-1.23; P =.1852).
In the safety analysis, 195 patients from the triplet arm and 204 from the doublet arm were included. The most common treatment-emergent adverse events (AEs) of grade 3/4 included thrombocytopenia (39% vs 17%), anemia (16% vs 10%, pneumonia (12% vs 10%), and fatigue (13% vs 1%), and these all occurred in higher incidences in the triplet arm compared with the control, respectively.
Treatment was discontinued in 41 (21%) of patients in the experimental arm versus 32 (16%) in the control arm due to treatment-emergent AEs. The most common reasons for treatment discontinuation included peripheral neuropathy (5%), fatigue (4%), nausea (3%), vomiting (2%), decreased appetite (2%), and thrombocytopenia (2%) in the triplet arm, and the most common reason in the control arm was peripheral neuropathy (7%).
The median time to treatment discontinuation was 194 days (IQR, 100-332) in the experimental arm versus 184 (IQR, 106-276) in the control arm, and among all patients who had discontinued, 19 (46%) in the once-per-week arm and 16 (50%) in the bortezomib and dexamethasone arm were over the age of 70 years.
Dose modifications were common in the triplet arm, occurring in 173 (89%) of patients compared with 156 (76%). Most of the side effects that were associated with selinexor were reversible and were mitigated with standard supportive care.
Serious AEs occurred in 101 (52%) of patients in the once-per-week arm versus 77 (38%) in the control arm, and the most frequent serious AE was pneumonia, occurring in 12% of each arm.
Overall, this study demonstrated a significant increase in PFS for patients previously treated with multiple myeloma when treated with the triplet versus the control arm of bortezomib with dexamethasone. The benefit was observed across subgroups, and the improved efficacy was particularly notable in that it was achieved during the first 24 weeks of therapy, according to the study authors.
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):P1563-1573. doi: 10.1016/S0140-6736(20)32292-3