Results from a phase III clinical trial (BOSTON) evaluating selinexor (Xpovio®) in combination with bortezomib (Velcade®) and dexamethasone for the treatment of relapsed or refractory myeloma patients have been published in the Lancet.
The data provide evidence to support the use of selinexor for the treatment of relapsed or refractory myeloma patients who had received one to three prior lines of therapy.
- Selinexor, bortezomib and dexamethasone (SVd) reduced the risk of disease progression by 30% compared to treatment with bortezomib and dexamethasone (Vd) alone.
- The most common serious adverse effects were thrombocytopenia, anaemia, and fatigue.
The trial compared SVd to Vd for the treatment of relapsed or refractory myeloma patients who had received one to three prior lines of treatment including proteasome inhibitors. It recruited 407 relapsed or refractory myeloma patients across 123 sites in 21 countries.
The median progression-free survival (PFS) was 13.93 months in the SVd group, compared with 9.46 months in the Vd control group. The overall response rate was significantly higher in the selinexor, bortezomib, and dexamethasone group (76·4% [95% CI 69·8–82·2]) than in the bortezomib and dexamethasone group (62·3% [55·3–68·9]).
Efficacy was consistent across various patient subgroups, including older, less fit patients and patients who had received previous lenalidomide treatment.
The combination of SVd used 40% less bortezomib and 25% less dexamethasone during the first 24 weeks of treatment. The once-weekly regimen also offers a convenient treatment option by reducing clinic visits by around 37% compared with standard Vd doublet regimens and other commonly used triplet regimens containing Vd.
Adverse events were consistent with those previously reported from other selinexor studies. Most were manageable with dose modifications and/or standard supportive care. The most common serious adverse effects (grade 3 or 4) were thrombocytopenia (39%), anaemia (16%), and fatigue (13%). The most common non-haematologic treatment-related adverse events were nausea (50%), fatigue (42%), decreased appetite (35%), and diarrhoea (32%) and were mostly Grade one and two events.
Peripheral neuropathy (PN) rates were significantly lower on SVd compared to Vd (32.3% vs. 47.1%; p=0.0010). In addition, PN rates of grade ≥2 were also significantly lower in the SVd arm compared to Vd (21.0% vs. 34.3%, P=0.0013).
The results indicate that the addition selinexor to bortezomib and dexamethasone was well tolerated and reduced the risk of disease progression in relapsed or refractory patients.
Selinexor may be available through an expanded access programme for relapsed and/or refractory patients who have limited treatment options. To find out more, healthcare professionals can contact KEAP_selinexor@caligorrx.com.