Selinexor in combination with decitabine in patients with acute myeloid leukemia: results from a phase 1 study
| Autor: | William Blum, John C. Byrd, Sumithira Vasu, Gregory K. Behbehani, Rebecca B. Klisovic, Karilyn Larkin, Ramiro Garzon, Amy S. Ruppert, Alice S. Mims, Qiuhong Zhao, James S. Blachly, Shelley Orwick, Bhavana Bhatnagar, Christopher C. Oakes, Parvathi Ranganathan, Alison Walker |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Adult
Oncology Cancer Research medicine.medical_specialty Decitabine Article Unmet needs 03 medical and health sciences 0302 clinical medicine Refractory hemic and lymphatic diseases Internal medicine medicine Humans In patient Aged business.industry Treatment options Myeloid leukemia Hematology Triazoles Clinical trial Leukemia Myeloid Acute Hydrazines 030220 oncology & carcinogenesis Azacitidine business 030215 immunology medicine.drug |
| Zdroj: | Leuk Lymphoma |
| ISSN: | 1029-2403 1042-8194 |
| Popis: | 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/m(2), 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 60mg (~35 mg/m(2)) 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 60mg, twice-weekly for two weeks after decitabine, improved tolerability of the regimen and demonstrated preliminary clinical activity in poor-risk patients with AML. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|