A Phase 2 study of combination therapy with arsenic trioxide and gemtuzumab ozogamicin in patients with myelodysplastic syndromes or secondary acute myeloid leukemia

Authors

  • Mikkael A. Sekeres MD, MS,

    Corresponding author
    1. Leukemia Program, Department of Hematologic Oncology and Blood Disorders, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio
    • Leukemia Program, Department of Hematologic Oncology and Blood Disorders, Cleveland Clinic Taussig Cancer Institute, Desk R35, 9500 Euclid Avenue, Cleveland, OH 44195
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    • Fax: (216) 636-0636

  • Jaroslaw P. Maciejewski MD, PhD,

    1. Leukemia Program, Department of Hematologic Oncology and Blood Disorders, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio
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  • Harry P. Erba MD,

    1. University of Michigan, Ann Arbor, Michigan
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  • Manuel Afable MD,

    1. Leukemia Program, Department of Hematologic Oncology and Blood Disorders, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio
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  • Ricki Englehaupt,

    1. Leukemia Program, Department of Hematologic Oncology and Blood Disorders, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio
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  • Ronald Sobecks MD,

    1. Leukemia Program, Department of Hematologic Oncology and Blood Disorders, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio
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  • Anjali Advani MD,

    1. Leukemia Program, Department of Hematologic Oncology and Blood Disorders, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio
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  • Sherry Seel,

    1. Leukemia Program, Department of Hematologic Oncology and Blood Disorders, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio
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  • Josephine Chan PhD,

    1. Leukemia Program, Department of Hematologic Oncology and Blood Disorders, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio
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  • Matt E. Kalaycio MD

    1. Leukemia Program, Department of Hematologic Oncology and Blood Disorders, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio
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  • Presented in part at the American Society of Hematology Annual Meeting; December 9–12, 2006; Atlanta, GA and published as Sekeres MA, Maciejewski J, Erba H, Sobecks R, Advani A, Nichols J, Chen J. A phase II trial of combination therapy with arsenic trioxide (ATO) and gemtuzumab ozogamicin (GO) in patients with high-risk myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML) arising from MDS [poster]. Blood 2006;108:754a.

Abstract

BACKGROUND:

Higher-risk myelodysplastic syndromes (MDS) are similar pathobiologically to acute myeloid leukemia (AML), particularly in older adults. AML therapies thus may have activity in MDS. In the current study, phase 2 study data of arsenic trioxide (ATO) and gemtuzumab ozogamicin (GO) in CD33-positive patients with MDS and secondary AML (sAML) were presented.

METHODS:

Between June 2004 and February 2006, 30 patients with higher-risk MDS or sAML received ATO (at a dose of 0.25 mg/kg intravenously for 5 days during Week 1, then twice weekly during Weeks 2-12) and GO (at a dose of 3 mg/m2 on Day 8) for 1 or 2 cycles of 12 weeks each. The primary endpoint was response as per MDS or AML International Working Group (IWG) criteria. Adverse events were collected throughout treatment. Patients were followed for a minimum of 3 years for survival.

RESULTS:

The median patient age was 69 years. A total of 18 patients had MDS, 12 had sAML, and 19 had been previously treated. Seventeen patients (57%) completed ≥1 cycle, and 7 patients (23%) completed 2 cycles. IWG responses occurred in 9 patients (30%) according to IWG MDS criteria (including 2 of 7 patients who failed hypomethylating agents) and 3 of 12 AML patients (25%) according to IWG AML criteria. Grade 3/4 (according to National Cancer Institute Common Toxicity Criteria [version 3.0]) thrombocytopenia occurred in 47% of patients, neutropenia in 63%, and anemia in 37% of patients. The median overall survival was 9.7 months (28.6 months in responders and 7.6 months in nonresponders; P <.001). Patients who completed 2 cycles of therapy spent a median of 13 days in the hospital.

CONCLUSIONS:

Combination therapy with ATO and GO was found to have acceptable response rates and toxicity, and may be a viable treatment option to standard induction therapy, particularly for patients who fail therapy with hypomethylating agents. Cancer 2011. © 2010 American Cancer Society.

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