Selinexor in combination with decitabine in patients with acute myeloid leukemia: results from a phase 1 study.
Leuk Lymphoma
; 61(2): 387-396, 2020 02.
Article
em En
| MEDLINE
| ID: mdl-31545113
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 (â¼35 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.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Azacitidina
/
Leucemia Mieloide Aguda
Tipo de estudo:
Guideline
Limite:
Adult
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Aged
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Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article