Abstract
Decitabine may open the chromatin structure of leukemia cells making them accessible to the calicheamicin epitope of gemtuzumab ozogamicin (GO). A total of 110 patients (median age 70 years; range 27–89 years) were treated with decitabine and GO in a trial designed on model-based futility to accommodate subject heterogeneity: group 1: relapsed/refractory acute myeloid leukemia (AML) with complete remission duration (CRD) <1 year (N=28, 25%); group 2: relapsed/refractory AML with CRD ⩾1 year (N=5, 5%); group 3: untreated AML unfit for intensive chemotherapy or untreated myelodysplastic syndrome (MDS) or untreated myelofibrosis (MF; N=57, 52%); and group 4: AML evolving from MDS or relapsed/refractory MDS or MF (N=20, 18%). Treatment consisted of decitabine 20 mg/m2 daily for 5 days and GO 3 mg/m2 on day 5. Post-induction therapy included five cycles of decitabine+GO followed by decitabine alone. Complete remission (CR)/CR with incomplete count recovery was achieved in 39 (35%) patients; group 1= 5/28 (17%), group 2=3/5 (60%), group 3=24/57 (42%) and group 4=7/20 (35%). The 8-week mortality in groups 3 and 4 was 16% and 10%, respectively. Common drug-related adverse events included nausea, mucositis and hemorrhage. Decitabine and GO improved the response rate but not overall survival compared with historical outcomes in untreated AML ⩾60 years.
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Acknowledgements
We thank Eisai Corporation for supporting the clinical trial. This study was conducted following the guidelines of The University of Texas MD Anderson Cancer Center after local IRB approval. It was supported in part by the MD Anderson Cancer Center Support Grant (CCSG) CA016672 and Eisai Corporation.
Author contributions
ND and GB wrote the paper; GB and HK designed and coordinated the study; MK, SO, AF, SV, TK, EJ, NP, CD, JC, GB, HK enrolled the patients and conducted the research; and ND, GB, XW, SP analyzed the data and performed the statistics. All of the authors participated in the discussion, have reviewed and approved the current version of the manuscript.
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GB received research funding from Eisai Corporation. The remaining authors declare no conflict of interest.
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Daver, N., Kantarjian, H., Ravandi, F. et al. A phase II study of decitabine and gemtuzumab ozogamicin in newly diagnosed and relapsed acute myeloid leukemia and high-risk myelodysplastic syndrome. Leukemia 30, 268–273 (2016). https://doi.org/10.1038/leu.2015.244
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DOI: https://doi.org/10.1038/leu.2015.244
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