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Safety, efficacy and biological predictors of response to sequential azacitidine and lenalidomide for elderly patients with acute myeloid leukemia.
- Source :
-
Leukemia [Leukemia] 2012 May; Vol. 26 (5), pp. 893-901. Date of Electronic Publication: 2011 Oct 28. - Publication Year :
- 2012
-
Abstract
- Acute myeloid leukemia (AML) is a disease of the elderly. Poor outcomes with standard therapies necessitate novel approaches. Outpatient regimens sufficiently potent and well tolerated to induce remissions and enable continuation therapy may be beneficial. In this phase-1 study, we determined the maximum tolerated dose (MTD) and the efficacy for sequential azacitidine and lenalidomide as remission induction and continuation therapy in elderly, previously untreated patients. We investigated the impact on global DNA methylation and bone marrow cytokines, and sought biological predictors of response. Eighteen patients were enrolled. The MTD was not reached. Median follow-up was 8.2 months (10.3 months for survivors). Common adverse events included fatigue, injection site reactions, constipation, nausea, pruritus and febrile neutropenia. Ten patients responded (56%), and the rate of complete remissions (CRs) or CRs with incomplete recovery of blood counts for evaluable patients was 44% (7/16). The median response duration was 6.2 months. DNA demethylation and changes in bone marrow cytokines were observed; responders had a unique cytokine profile and a trend towards lower methylation levels. Sequential azacitidine and lenalidomide was well tolerated with encouraging clinical and biological activity in previously untreated elderly AML patients. This trial is registered at ClinicalTrials.gov (NCT00890929).
- Subjects :
- Aged
Aged, 80 and over
Antineoplastic Combined Chemotherapy Protocols administration & dosage
Antineoplastic Combined Chemotherapy Protocols adverse effects
Azacitidine administration & dosage
Cohort Studies
Cytokines genetics
Cytokines metabolism
DNA Methylation
Female
Gene Expression Profiling
Humans
Lenalidomide
Leukemia, Myeloid, Acute genetics
Male
Maximum Tolerated Dose
Middle Aged
Mutation
Thalidomide administration & dosage
Thalidomide analogs & derivatives
Treatment Outcome
Antineoplastic Combined Chemotherapy Protocols therapeutic use
Leukemia, Myeloid, Acute drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1476-5551
- Volume :
- 26
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Leukemia
- Publication Type :
- Academic Journal
- Accession number :
- 22033493
- Full Text :
- https://doi.org/10.1038/leu.2011.294