Combination therapy with selinexor appears safe, effective in AML

SAN DIEGO — The use of selinexor in combination with high-dose cytarabine and mitoxantrone demonstrated promising overall response rates in patients with acute myeloid leukemia, according to findings presented at the ASH Annual Meeting and Exposition.

Amy Wang, MD, from the University of Chicago Medical Center, and colleagues conducted a phase 1 dose-escalation study with cohort expansion in 20 patients with AML. Increasing doses of selinexor (KPT-330, Karyopharm Therapeutics) were given in addition to high-dose cytarabine and mitoxantrone to assess the safety and efficacy of the combination as well as the maximum tolerated dose of selinexor.

Seventeen patients were administered selinexor at 80 mg, while the remaining patient population was administered selinexor at 60 mg. Seventy percent of the patient population was female and the patient population had a median age of 61 years. At enrollment, 60% of the patient population had newly diagnosed AML.

Patients were first placed on an induction regimen that lasted 12 days and consisted of high-dose cytarabine and mitoxantrone given on days 1 and 5, and selinexor given twice-weekly at days 2, 4, 9 and 11. Patients who did respond to the induction regimen then proceeded to either consolidation or maintenance therapy.

Consolidation therapy consisted of selinexor at days 2, 4, 9 and 11 in combination with high-dose cytarabine at days 1, 3 and 5 for up to 4 cycles. On maintenance therapy, patients received selinexor weekly for up to 1 year.

The researchers observed dose limiting toxicity in the patient population for up to 56 days. Using the NCI Common Terminology Criteria for Adverse Events, any grade 3 or greater treatment-related, non-hematologic toxicity other than nausea, vomiting and liver function abnormalities at less than 48 hours after treatment or electrolyte abnormalities correctable with therapy, was considered dose limiting.

Nineteen of the patients completed induction therapy. The overall response rate in the patient population was 68.4% and the complete remission with incomplete count recovery rate was 63%.

Ninety-one percent of patients with newly diagnosed AML and 80% of patients aged 60 years and younger reached an ORR.

Forty-seven percent of patients reached a complete response.

The patient population experienced 68 adverse events during the phase 1 study. The most common grade 1 and grade 2 adverse events included diarrhea (32%), anorexia (26%) and nausea/vomiting (21%).

Seventy-four percent of patients experienced grade 3 febrile neutropenia and 26% of patients experienced a serious adverse event.

“The combination of selinexor with high-dose cytarabine and mitoxantrone was well tolerated and the recommended phase 2 dosing of selinexor is 80 mg,” Wang said during the presentation.

Wang acknowledged that the results from this study warrant further investigation in a larger study. – by Ryan McDonald

Reference: Wang A, et al. Abstract 212. Presented at: ASH Annual Meeting and Exposition; Dec. 3-6, 2016; San Diego.

Disclosure: Wang reports no relevant financial disclosures. Please see the full study for a list of all other relevant financial disclosures.