What do we know about Selinexor’s activity in myeloma?
Selinexor alone and in combination with dexamethasone is being evaluated in an ongoing Phase I study in patients with advanced multiple myeloma or other blood cancers. Twice-weekly selinexor in combination with low-dose dexamethasone demonstrated high rates of durable responses in patients with heavily pre-treated and refractory multiple myeloma. [Chen ASH 2014 #4473]
- In the nine evaluable patients with refractory multiple myeloma, a 67% overall response rate (partial response or better) was seen, with one stringent complete response (sCR, 11%) and five partial responses (PR, 56%).
- The overall median duration of response, which measures time from response to progression, was approximately 7 months.
- The most common adverse events were nausea, fatigue, weight loss, and vomiting.
- During the dose evaluation part of the study, 45 mg/m2 of selinexor was determined to be the maximum tolerated dose. Based on these results, a fixed dose of 80 mg will be used for future studies of selinexor and low-dose dexamethasone in multiple myeloma.
In the laboratory, the combination of selinexor and the proteasome inhibitor carfilzomib (Kyprolis®, Onyx Pharmaceuticals) appear to act synergistically to kill myeloma cells. [Rosebeck ASH #3443] A Phase 1/2 study is evaluating the tolerability and efficacy of the combination of selinexor, Kyprolis, and low-dose dexamethasone. In the first three treated patients, all of whom have myeloma refractory to Kyprolis and dexamethasone, the three-drug combination induced one very good partial response (VGPR) and two PRs.