Evaluating the Efficacy in the BOSTON Trial for Multiple Myeloma

Binod Dhakal, MD, associate professor of medicine in the Division of Hematology at the Medical College of Wisconsin, discusses the BOSTON trial (NCT03110562) of selinexor (Xpovio) combination therapy in patients with relapsed/refractory multiple myeloma.

The BOSTON trial utilized a once-weekly administration of both selinexor and bortezomib (Velcade) within a 35-day cycle, according to Dhakal, a key differentiator from previous standard regimens that relied on a more frequent, twice-weekly schedule. This approach was not only effective but also aimed to improve patient quality of life and manageability by potentially reducing the treatment burden and clinic visits associated with traditional biweekly bortezomib dosing.

There was statistically significant improvement in median progression-free survival (PFS) and a longer duration of response, Dhakal says. Despite the known adverse event (AE) profile of selinexor, the study notes that the rate of grade 3/4 AEs was not significantly different for the selinexor combination vs bortezomib/dexamethasone alone.

TRANSCRIPTION

0:10 | The BOSTON trial is a phase 3 trial. The way it is designed is that patients are [randomly assigned] 1:1 to either selinexor with bortezomib and dexamethasone, in 35-day cycles where selinexor is given at 100 mg on day 1, 8, 15, 22, and 29 and bortezomib is given weekly. This is a little bit different than the other registrational trial where bortezomib was given. Usually, it is given twice a week. So what is done here is it given [on day] 1, 8, 15, and 22, exactly on the same day of selinexor. Dexamethasone is given on [day] 1, 2, 8, 9, 15, [etc] in that fashion. Those [randomly assigned] to bortezomib and dexamethasone, bortezomib is given twice weekly here, 1.3 mg/m² [on days] 1, 4, 8, 11 on 21-day cycles, for cycles 1 to 8 and after that 35-day cycles, where bortezomib is given weekly. Now, in both the cases, the treatment is given until progression.

1:06 | The primary end point of the study is PFS, and there were a number of secondary end points like response rate, depth of response, overall survival, and so forth. When you look at the baseline characteristics, they were pretty well balanced. When you look at overall response rate, [bortezomib]/dexamethasone response rate was 77%. In the selinexor arm, it is 62% and the median duration of response was 20 months vs 13 months. The median PFS is almost 14 months with selinexor combination vs 9 months, which is statistically significant.

1:33 | Now in terms of [AEs], the most common [AEs], as we all know with the selinexor-based combination are cytopenia, nausea and some gastrointestinal [AEs]. Because of the dose given once a week, if you look at the [AE] profile, the grade 3/4 [AEs] were not significantly different in the 2 arms. For example, thrombocytopenia is seen 39% in selinexor combination vs 35%, and similarly the other cytopenias were also more or less comparable.