Phase 2 study of epigenetic priming with decitabine followed by cytarabine for acute myeloid leukemia in older patients.
Annie P ImKevin QuannMounzer AghaAnastasios RaptisRobert L RednerJing-Zhou HouRafic FarahKathleen A DorritieAlison R SehgalDaniel NormolleDana H BovbjergNidhi AggarwalJames HermanKonstantinos LontosMichael BoyiadzisPublished in: American journal of hematology (2024)
Acute myeloid leukemia (AML) in older patients has a poor prognosis, low complete remission (CR) rates, and poor overall survival (OS). Preclinical studies have shown synergistic effects of epigenetic priming with hypomethylating agents followed by cytarabine. Based on these data, we hypothesized that an induction regimen using epigenetic priming with decitabine, followed by cytarabine would be effective and safe in older patients with previously untreated AML. Here, we conducted a phase 2 trial in which older patients with previously untreated AML received an induction regimen consisting of 1 or 2 courses of decitabine 20 mg/m 2 intravenously (IV) for 5 days followed by cytarabine 100 mg/m 2 continuous IV infusion for 5 days. Forty-four patients (median age 76 years) were enrolled, and CR/CRi was achieved by 26 patients (59% of all patients, 66.7% of evaluable patients). Fourteen of 21 (66.7%) patients with adverse cytogenetics achieved CR including six out of seven evaluable patients with TP53 mutations. The 4- and 8-week mortality rates were 2.3% and 9.1%, respectively, with median OS of 10.7 months. These results suggest epigenetic priming with decitabine followed by cytarabine should be considered as an option for first-line therapy in older patients with AML. This trial was registered at www.clinicaltrials.gov as # NCT01829503.
Keyphrases
- acute myeloid leukemia
- end stage renal disease
- allogeneic hematopoietic stem cell transplantation
- chronic kidney disease
- ejection fraction
- poor prognosis
- newly diagnosed
- high dose
- dna methylation
- gene expression
- physical activity
- prognostic factors
- clinical trial
- type diabetes
- rheumatoid arthritis
- peritoneal dialysis
- stem cells
- low dose
- emergency department
- bone marrow
- machine learning
- big data
- cardiovascular events
- risk factors
- artificial intelligence
- electronic health record
- patient reported
- placebo controlled