Multiple myeloma patients who received several prior lines of therapy showed promising response rates when treated with a combination of Karyopharm Therapeutics‘ selinexor and dexamethasone, a Phase 1 trial showed.
While only 4% of patients receiving selinexor treatment alone achieved a partial response, combining selinexor – at a 45 mg/m2 dose – with dexamethasone increased the response rate to 50%. Among the six patients who responded to the combination, one had a complete eradication of their tumor.
The study, “Safety and efficacy of selinexor in relapsed or refractory multiple myeloma and Waldenstrom’s macroglobulinemia,” was published in Blood.
Selinexor (KPT-330) is an oral selective inhibitor of nuclear export (SINE) that targets the XPO1 protein. By inhibiting nuclear export, selinexor promotes the accumulation of tumor-suppressing proteins inside the nucleus of cancer cells, inducing their death while sparing healthy cells.
The trial (NCT01607892) evaluated the safety and efficacy of selinexor alone and in combination with dexamethasone in patients with heavily-treated, refractory myeloma and Waldenstrom’s macroglobulinemia (WM), a type of non-Hodgkin’s lymphoma.
Among the 84 patients included, 81 had myeloma and had received at least three lines of therapy. The three WM patients had received at least two prior treatment regimens.
Fifty-seven patients received ascending doses of selinexor alone – ranging from 3 mg/m2 to 60 mg/m2 – and 27 received selinexor – at 45 mg/m2 or 60 mg/m2 doses – together with 20 mg of dexamethasone. Different treatment schedules, such as three times weekly and two times weekly, were also tested.
Overall, 25% of patients had some sort of benefit from the treatment. However, only one patient experienced a complete response (undetectable cancer cells) and seven showed a partial response.
When selinexor was given alone, only 4% of patients saw a reduction in their tumor burden. But for those who received twice weekly 45 mg/m2 selinexor plus dexamethasone, the overall response rate was 50%.
Three of eight patients who responded – including one with a complete response – had previously been treated with Velcade (bortezomib), Kiprolis (carfilzomib), Revlimid (lenalidomide), and Pomalyst (pomalidomide).
The most common adverse effects were nausea, fatigue, anorexia, vomiting, weight loss, and diarrhea, which were mainly mild to moderate in severity. The most severe adverse event reported was low levels of platelets.
“Selinexor is an oral agent with a completely novel mechanism of action and anti-[myeloma] activity in combination with dexamethasone that could provide a new option for patients suffering from this incurable disease,” the researchers said.
Given the activity of selinexor in combination with dexamethasone in heavily-treated patients, the combination is now being tested in the Phase 2 STORM trial (NCT02336815).
Selinexor is also being evaluated in combination with standard myeloma treatments in the Phase 1/2 STOMP trial (NCT02343042).
Preliminary data of both trials continue to demonstrate the positive effects of selinexor, with good safety and tolerability profiles, both as a single agent or in combination with other therapies.
Karyopharm also started the pivotal BOSTON Phase 3 trial (NCT03110562) to evaluate selinexor in combination with Velcade plus dexamethasone for the treatment of relapsed or refractory myeloma patients. The trial is currently recruiting participants and topline data is expected during 2019.