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Efficacy of the hypomethylating agents as frontline, salvage, or consolidation therapy in adults with acute myeloid leukemia (AML)

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Abstract

The hypomethylating agents (HAs), azacitidine and decitabine, have emerged as an alternative to initial and salvage therapy in patients with acute myeloid leukemia (AML). Little is known about how AML responds to hypomethylating agents after standard therapy, and the activity of these agents in a real-world setting is not well studied. We retrospectively examined data for 75 consecutive AML patients at Wake Forest from 2002 to 2011 treated with HAs either as first-line (n = 34), salvage (n = 28), or consolidation (n = 13) therapy. We collected data on age, gender, race, Charlson comorbidity index (CCI), cytogenetics, type of treatment, complete remission (CR), complete remission with incomplete count recovery (CRi), and survival. Statistical analysis was performed using Kaplan–Meier estimates and Cox proportional hazards models. Frontline response rate (CR + CRi) was 26.5 %, and median overall survival (OS) was 3.4 months (95 % CI 1.3–7.4), with 18 % alive at 1 year. In the salvage cohort, the response rate was significantly lower compared to frontline (3.6 versus 26.5 %, p = 0.017). Despite the reduced response, OS from time of HA treatment was longer than frontline at 8.2 months (CI 4.8–10.3). In the consolidation cohort, OS was 13.8 months (CI 8.0–21.6) with one patient in remission more than 30 months from diagnosis. These data suggest that prior cytotoxic therapy decreases marrow response rates to HAs but not survival. Furthermore, use of hypomethylating agents for consolidation resulted in a median overall survival over 1 year in a cohort of older patients. This suggests that hypomethylating agents have activity in all phases of AML treatment.

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Acknowledgments

The authors would like to acknowledge Karen Klein for her critical reading of the manuscript; TSP is supported by NCI 1K08CA169809-01, SI is supported by NCI Cancer Center Support Grant (CCSG) P30CA012197, and HDK is supported by NIA K23AG038361.

Conflict of interest

The authors declare no competing financial interests.

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Authors and Affiliations

  1. Internal Medicine, Wake Forest Baptist Health, Winston-Salem, NC, USA

    Bernard Tawfik, Sarunas Sliesoraitis & Scott Isom

  2. Section on Hematology and Oncology, Internal Medicine, Wake Forest Baptist Health, Winston-Salem, NC, USA

    Susan Lyerly, Heidi D. Klepin, Julia Lawrence, Scott Isom, Leslie R. Ellis, Megan Manuel, Sarah Dralle, Dmitriy Berenzon, Bayard L. Powell & Timothy Pardee

  3. Cancer Biology, Comprehensive Cancer Center of Wake Forest University, Medical Center Blvd, Winston-Salem, NC, 27157, USA

    Timothy Pardee

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  1. Bernard Tawfik
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Correspondence to Timothy Pardee.

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Tawfik, B., Sliesoraitis, S., Lyerly, S. et al. Efficacy of the hypomethylating agents as frontline, salvage, or consolidation therapy in adults with acute myeloid leukemia (AML). Ann Hematol 93, 47–55 (2014). https://doi.org/10.1007/s00277-013-1940-9

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  • DOI: https://doi.org/10.1007/s00277-013-1940-9

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