Safety, efficacy and biological predictors of response to sequential azacitidine and lenalidomide for elderly patients with acute myeloid leukemia

D. A. Pollyea, H. E. Kohrt, L. Gallegos, Maria Figueroa, O. Abdel-Wahab, B. Zhang, S. Bhattacharya, J. Zehnder, M. Liedtke, J. R. Gotlib, S. Coutre, C. Berube, A. Melnick, R. Levine, B. S. Mitchell, B. C. Medeiros

Research output: Contribution to journalArticle

62 Citations (Scopus)

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).

Original languageEnglish (US)
Pages (from-to)893-901
Number of pages9
JournalLeukemia
Volume26
Issue number5
DOIs
StatePublished - May 1 2012
Externally publishedYes

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Azacitidine
Acute Myeloid Leukemia
Safety
Maximum Tolerated Dose
Cytokines
Bone Marrow
Remission Induction
Febrile Neutropenia
DNA Methylation
Constipation
Pruritus
Nausea
Methylation
Fatigue
Survivors
Outpatients
Therapeutics
lenalidomide
Injections
DNA

Keywords

  • Elderly AML
  • methylation
  • phase one

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Safety, efficacy and biological predictors of response to sequential azacitidine and lenalidomide for elderly patients with acute myeloid leukemia. / Pollyea, D. A.; Kohrt, H. E.; Gallegos, L.; Figueroa, Maria; Abdel-Wahab, O.; Zhang, B.; Bhattacharya, S.; Zehnder, J.; Liedtke, M.; Gotlib, J. R.; Coutre, S.; Berube, C.; Melnick, A.; Levine, R.; Mitchell, B. S.; Medeiros, B. C.

In: Leukemia, Vol. 26, No. 5, 01.05.2012, p. 893-901.

Research output: Contribution to journalArticle

Pollyea, DA, Kohrt, HE, Gallegos, L, Figueroa, M, Abdel-Wahab, O, Zhang, B, Bhattacharya, S, Zehnder, J, Liedtke, M, Gotlib, JR, Coutre, S, Berube, C, Melnick, A, Levine, R, Mitchell, BS & Medeiros, BC 2012, 'Safety, efficacy and biological predictors of response to sequential azacitidine and lenalidomide for elderly patients with acute myeloid leukemia', Leukemia, vol. 26, no. 5, pp. 893-901. https://doi.org/10.1038/leu.2011.294
Pollyea, D. A. ; Kohrt, H. E. ; Gallegos, L. ; Figueroa, Maria ; Abdel-Wahab, O. ; Zhang, B. ; Bhattacharya, S. ; Zehnder, J. ; Liedtke, M. ; Gotlib, J. R. ; Coutre, S. ; Berube, C. ; Melnick, A. ; Levine, R. ; Mitchell, B. S. ; Medeiros, B. C. / Safety, efficacy and biological predictors of response to sequential azacitidine and lenalidomide for elderly patients with acute myeloid leukemia. In: Leukemia. 2012 ; Vol. 26, No. 5. pp. 893-901.
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