Selinexor in combination with decitabine in patients with acute myeloid leukemia: results from a phase 1 study.

ABSTRACT: Current treatment options for older and relapsed or refractory (R/R) acute myeloid leukemia (AML) patients are limited and represent an unmet need. Based on preclinical studies showing strong anti-leukemic effects in vivo, this phase I dose-escalation study assessed the safety and preliminary clinical activity of the oral exportin-1 inhibitor, selinexor, in combination with the hypomethylating agent, decitabine 20?mg/m², in adults with R/R AML and in older (age???60) untreated AML patients. There were no protocol-defined dose limiting toxicities. The recommended phase 2 dose of selinexor was 60?mg (?35?mg/m²) given twice-weekly. Notable grade ?3 toxicities included asymptomatic hyponatremia (68%), febrile neutropenia (44%), sepsis (44%), hypophosphatemia (36%), and pneumonia (28%). In 25 patients, the overall response rate was 40%. Modification of selinexor to a flat dose of 60?mg, twice-weekly for two weeks after decitabine, improved tolerability of the regimen and demonstrated preliminary clinical activity in poor-risk patients with AML.

SUBMITTER: Bhatnagar B 

PROVIDER: S-EPMC7552944 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature