Safety, efficacy and biological predictors of response to sequential azacitidine and lenalidomide for elderly patients with acute myeloid leukemia.
Summary of "Safety, efficacy and biological predictors of response to sequential azacitidine and lenalidomide for elderly patients with acute myeloid leukemia."
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).Leukemia advance online publication, 28 October 2011; doi:10.1038/leu.2011.294.
Affiliation
Divisions of Oncology, Hematologic Malignancies and Bone Marrow Transplant, Department of Medicine, University of Colorado Cancer Center, Aurora, CO, USA.
Journal Details
This article was published in the following journal.
Name: Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K
ISSN: 1476-5551
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/22033493
- DOI: http://dx.doi.org/10.1038/leu.2011.294
Medical and Biotech [MESH] Definitions
Clinical Trial, Phase Iii
Work that is a report of a pre-planned, usually controlled, clinical study of the safety and efficacy of diagnostic, therapeutic, or prophylactic drugs, devices, or techniques after phase II trials. A large enough group of patients is studied and closely monitored by physicians for adverse response to long-term exposure, over a period of about three years in either the United States or a foreign country.
Adjuvants, Immunologic
Substances that augment, stimulate, activate, potentiate, or modulate the immune response at either the cellular or humoral level. The classical agents (Freund's adjuvant, BCG, Corynebacterium parvum, et al.) contain bacterial antigens. Some are endogenous (e.g., histamine, interferon, transfer factor, tuftsin, interleukin-1). Their mode of action is either non-specific, resulting in increased immune responsiveness to a wide variety of antigens, or antigen-specific, i.e., affecting a restricted type of immune response to a narrow group of antigens. The therapeutic efficacy of many biological response modifiers is related to their antigen-specific immunoadjuvanticity.
Safety
Freedom from exposure to danger and protection from the occurrence or risk of injury or loss. It suggests optimal precautions in the workplace, on the street, in the home, etc., and includes personal safety as well as the safety of property.
Biological Therapy
Treatment of diseases with biological materials or biological response modifiers, such as the use of GENES; CELLS; TISSUES; organs; SERUM; VACCINES; and humoral agents.
Treatment Outcome
Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, practicability, etc., of these interventions in individual cases or series.
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