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Acute Leukemias

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

Leukemia volume 26, pages 893–901 (2012)Cite this article

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).

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Acknowledgements

This study was supported by a research funding from Celgene who provided lenalidomide, but did not participate in the design and conduct of the study, collection, management, analysis or interpretation of the data, or preparation or approval of the manuscript. DAP was supported by a Leukemia and Lymphoma Society Career Development Award, an ASCO Young Investigator Award, an ASH research training award and a NIH/NCRR CTSA KL2 award #RR025743. The Stanford University Institute for Immunity, Transplantation and Infection assisted with cytokine data interpretation, and Holden Maecker and Yael Rosenberg in the Stanford Human Immune Monitoring Center performed the Luminex assays.

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Authors and Affiliations

  1. Divisions of Oncology, Department of Medicine, Hematologic Malignancies and Bone Marrow Transplant, University of Colorado Cancer Center, Aurora, CO, USA

    D A Pollyea

  2. Department of Medicine, Stanford University Cancer Center, Stanford, CA, USA

    H E Kohrt, L Gallegos, B Zhang, S Bhattacharya, J Zehnder, M Liedtke, J R Gotlib, S Coutre, C Berube, B S Mitchell & B C Medeiros

  3. Department of Pathology, University of Michigan School of Medicine, Ann Arbor, MI, USA

    M E Figueroa

  4. Department of Medicine, Leukemia Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    O Abdel-Wahab & R Levine

  5. Division of Hematology/Oncology, Department of Medicine, Weill Cornell Medical College, New York, NY, USA

    A Melnick

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  1. D A Pollyea
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Correspondence to D A Pollyea or B C Medeiros.

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Competing interests

BCM and ML receive research funds from Celgene. BCM receives consultation funds from Celgene.

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Pollyea, D., Kohrt, H., Gallegos, L. et al. Safety, efficacy and biological predictors of response to sequential azacitidine and lenalidomide for elderly patients with acute myeloid leukemia. Leukemia 26, 893–901 (2012). https://doi.org/10.1038/leu.2011.294

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