Effects of combined treatment with selinexor, carfilzomib and dexamethasone once a week in patients with relapsed/refractory multiple myeloma

This study evaluated the safety and effectiveness of selinexor (Xpovio) in combination with carfilzomib (Kyprolis) and dexamethasone (Decadron) (XKd) in patients with relapsed/refractory (r/r) multiple myeloma (MM) that still responded to carfilzomib. The data showed that weekly administered XKd was highly effective and well-tolerated in these patients.

Multiple myeloma (MM) is a cancer of plasma cells, a type of white blood cell. Patients who experience tumor growth after treatment are said to have relapsed. Those that are unresponsive to treatment are called refractory. Exportin 1 (XPO1) is a protein that has an important role in allowing cancer cells to escape destruction.

Selinexor is a new, oral drug that blocks XPO1, leading to the death of cancer cells. Based on recent favorable evidence of MM cell growth suppression, the Food and Drug Administration (FDA) has granted accelerated approval for the use of selinexor in combination with proteasome inhibitor (PI) bortezomib (Velcade) and steroid drug dexamethasone in patients with r/r MM.

Carfilzomib is a second-generation PI approved for combination treatment with dexamethasone for MM treatment. XKd has been shown to be tolerable and effective in heavily pretreated patients with MM, including those that are non-responsive to carfilzomib. There is a need to further investigate the safety and effectiveness of XKd in patients that are still responsive to carfilzomib.

This study included 32 patients previously treated for MM that were still responsive to carfilzomib. Patients received 80 mg or 100 mg of selinexor, 56 mg/m² or 70 mg/m² of carfilzomib, and 40 mg of dexamethasone, orally, once weekly. The average follow-up time was 15.1 months.

The established effective and well-tolerated doses were 80 mg selinexor, 56 mg/m² carfilzomib, and 40mg dexamethasone. Overall, 78.1% of patients responded to XKd treatment. 15.7% of patients had a complete response (complete disappearance of cancer cells), 28.1% had a very good partial response (tumor shrinkage) and 34.4% had a partial response.

The average duration of response was 22.7 months. The average survival without cancer worsening was 15 months. The average overall survival was not reached (exceeded the study duration). Common side effects included low blood cell counts, nausea, and fatigue.

The study showed that XKd treatment was well-tolerated and had good effectiveness in patients with r/r MM.

This study included a small number of participants and had a short follow-up period. It also did not have a comparison group. The study was funded by Karyopharm Therapeutics, Inc, the manufacturer of selinexor.