Effectiveness in Myeloma - Multiple Myeloma Research Foundation

MULTIPLE MYELOMA KNOWLEDGE CENTER

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.