A  regimen of selinexor and bortezomib once weekly combined with twice-weekly dexamethasone is an effective and convenient option for previously treated patients with multiple myeloma (MM), according to results reported in the Lancet.

In the ongoing, open-label, phase 3 Boston (Bortezomib, Selinexor and Dexamethasone) trial (ClinicalTri-als.gov Identifier: NCT03110562), investigators at 123 sites in 21 countries randomly assigned 402 patients in a 1:1 fashion to receive selinexor (Xpovio, Karyopharm), bortezomib and dexamethasone (SVd) (n=195) or bortezomib and dexamethasone (Vd) (n=207) (Lancet 2020;396[10262]:1563-1573). The patients, who were 18 years and older, previously had been treated with one to three lines of therapy, including proteasome inhibitors. Nearly half of the patients (48%) had high-risk cytogenetic abnormalities.

The SVd regimen was selinexor (100 mg once weekly), bortezomib (1.3 mg/m² once weekly) and dexamethasone (20 mg twice weekly), and the Vd regimen was bortezomib (1.3 mg/m² twice weekly for the first 24 weeks, then once weekly) and dexamethasone (20 mg four times weekly for the first 24 weeks, then twice weekly). The primary end point was progression-free survival (PFS) in the intent-to-treat population. The safety population included all patients who had received at least one dose of therapy. All responses were confirmed by an independent review committee.

Median PFS was 13.9 months (95% CI, 11.7 months to not evaluable) with SVd and 9.5 months (95% CI, 8.1-10.8 months) with Vd (hazard ratio, 0.70; 95% CI, 0.53-0.93; P=0.0075). The overall response rate (ORR) was 76.4% in the SVd group and 62.3% in the Vd group (P=0.0012). In addition, among patients who had received only one prior line of therapy, ORR was higher among those treated with SVd (80.8%, vs. 65.7% with Vd; P=0.0082). 

In addition, 16.9% of patients receiving SVd achieved a complete response or a stringent complete response versus 10.6% of those receiving Vd. SVd therapy also resulted in a significantly higher rate of deep responses (at least very good partial response) (44.6% vs. 32.4%; P=0.0082). Median overall survival for the SVd arm had not yet been reached as of the data cut-off date, whereas the median OS for the Vd arm was 25 months. The median OS for the SVd arm will be reported once it is reached.

The most frequent grade 3 to 4 adverse events in those receiving SVd compared with those receiving Vd were thrombocytopenia (39% vs. 17%), fatigue (13% vs. 1%], anemia (16% vs. 10%) and pneumonia (11% vs. 11%). Grade 2 or higher peripheral neuropathy was less frequent among those receiving SVd than those receiving Vd (21% vs. 34%; odds ratio, 0.50; 95% CI, 0.32-0·79; P=0.0013). In addition, 24% of patients in the SVd group and 30% of those in the Vd group died.

“SVd reduced the risk of disease progression or death by 30% and induced a higher rate of overall and deep responses compared to patients receiving a standard twice-weekly … regimen (Vd),” commented Paul Richardson, MD, a co-senior author of the study, in a press release. He noted that these benefits were seen although the SVd patients received approximately 40% less bortezomib and 25% less dexamethasone and had approximately 35% fewer clinic visits. “The efficacy of the SVd regimen was consistent and noteworthy across several key subgroups,” noted Richardson, the clinical program leader and director of clinical research at Dana-Farber Cancer Institute’s Jerome Lipper Multiple Myeloma Center, in Boston. These groups included those who were 65 years of age and older, were frail, had high-risk cytogenetics, or had moderate renal impairment, as well as those who previously had received either bortezomib or lenalidomide (Revlimid, Celgene) treatment. 

A limitation of the study he and his co-investigators acknowledged was the open-label design. However, they noted that “although physicians and patients were aware of their study treatments, to avoid bias, efficacy assessments were based solely on laboratory test results and were evaluated by an independent review committee that was masked to the treatment groups.”

Pointing out that in clinical practice bortezomib is most commonly administered once weekly, the investigators, noted that “these results are therefore directly applicable to standard multiple myeloma therapies used outside of clinical trials.”

—Sarah Tilyou

The Boston trial was funded by Karyopharm.