Identification of Patients With Acute Myeloblastic Leukemia Who Benefit From the Addition of Gemtuzumab Ozogamicin: Results of the MRC AML15 Trial

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Identification of Patients With Acute Myeloblastic Leukemia Who Benefit From the Addition of Gemtuzumab Ozogamicin: Results of the MRC AML15 Trial. / Burnett, AK; Hills, Robert; Milligan, Donald; Kjeldsen, L; Kell, J; Russell, NH; Yin, JAL; Hunter, A; Goldstone, AH; Wheatley, Keith.

In: Journal of Clinical Oncology, Vol. 29, No. 4, 01.02.2011, p. 369-377.

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Burnett, AK ; Hills, Robert ; Milligan, Donald ; Kjeldsen, L ; Kell, J ; Russell, NH ; Yin, JAL ; Hunter, A ; Goldstone, AH ; Wheatley, Keith. / Identification of Patients With Acute Myeloblastic Leukemia Who Benefit From the Addition of Gemtuzumab Ozogamicin: Results of the MRC AML15 Trial. In: Journal of Clinical Oncology. 2011 ; Vol. 29, No. 4. pp. 369-377.

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@article{5221933304bf403189758e60381fd2a0,
title = "Identification of Patients With Acute Myeloblastic Leukemia Who Benefit From the Addition of Gemtuzumab Ozogamicin: Results of the MRC AML15 Trial",
abstract = "Purpose Antibody-directed chemotherapy for acute myeloid leukemia (AML) may permit more treatment to be administered without escalating toxicity. Gemtuzumab ozogamicin (GO) is an immunoconjugate between CD33 and calicheamicin that is internalized when binding to the epitope. We previously established that it is feasible to combine GO with conventional chemotherapy. We now report a large randomized trial testing the addition of GO to induction and/or consolidation chemotherapy in untreated younger patients. Patients and Methods In this open-label trial, 1,113 patients, predominantly younger than age 60 years, were randomly assigned to receive a single dose of GO (3 mg/m(2)) on day 1 of induction course 1 with one of the following three induction schedules: daunorubicin and cytarabine; cytarabine, daunorubicin, and etoposide; or fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin. In remission, 948 patients were randomly assigned to GO in course 3 in combination with amsacrine, cytarabine, and etoposide or high-dose cytarabine. The primary end points were response rate and survival. Results The addition of GO was well tolerated with no significant increase in toxicity. There was no overall difference in response or survival in either induction of consolidation. However, a predefined analysis by cytogenetics showed highly significant interaction with induction GO (P = .001), with significant survival benefit for patients with favorable cytogenetics, no benefit for patients with poor-risk disease, and a trend for benefit in intermediate-risk patients. An internally validated prognostic index identified approximately 70% of patients with a predicted benefit of 10% in 5-year survival. Conclusion A substantial proportion of younger patients with AML have improved survival with the addition of GO to induction chemotherapy with little additional toxicity. J Clin Oncol 29: 369-377. (c) 2010 by American Society of Clinical Oncology",
author = "AK Burnett and Robert Hills and Donald Milligan and L Kjeldsen and J Kell and NH Russell and JAL Yin and A Hunter and AH Goldstone and Keith Wheatley",
year = "2011",
month = feb,
day = "1",
doi = "10.1200/JCO.2010.31.4310",
language = "English",
volume = "29",
pages = "369--377",
journal = "Journal of Clinical Oncology ",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "4",

}

RIS

TY - JOUR

T1 - Identification of Patients With Acute Myeloblastic Leukemia Who Benefit From the Addition of Gemtuzumab Ozogamicin: Results of the MRC AML15 Trial

AU - Burnett, AK

AU - Hills, Robert

AU - Milligan, Donald

AU - Kjeldsen, L

AU - Kell, J

AU - Russell, NH

AU - Yin, JAL

AU - Hunter, A

AU - Goldstone, AH

AU - Wheatley, Keith

PY - 2011/2/1

Y1 - 2011/2/1

N2 - Purpose Antibody-directed chemotherapy for acute myeloid leukemia (AML) may permit more treatment to be administered without escalating toxicity. Gemtuzumab ozogamicin (GO) is an immunoconjugate between CD33 and calicheamicin that is internalized when binding to the epitope. We previously established that it is feasible to combine GO with conventional chemotherapy. We now report a large randomized trial testing the addition of GO to induction and/or consolidation chemotherapy in untreated younger patients. Patients and Methods In this open-label trial, 1,113 patients, predominantly younger than age 60 years, were randomly assigned to receive a single dose of GO (3 mg/m(2)) on day 1 of induction course 1 with one of the following three induction schedules: daunorubicin and cytarabine; cytarabine, daunorubicin, and etoposide; or fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin. In remission, 948 patients were randomly assigned to GO in course 3 in combination with amsacrine, cytarabine, and etoposide or high-dose cytarabine. The primary end points were response rate and survival. Results The addition of GO was well tolerated with no significant increase in toxicity. There was no overall difference in response or survival in either induction of consolidation. However, a predefined analysis by cytogenetics showed highly significant interaction with induction GO (P = .001), with significant survival benefit for patients with favorable cytogenetics, no benefit for patients with poor-risk disease, and a trend for benefit in intermediate-risk patients. An internally validated prognostic index identified approximately 70% of patients with a predicted benefit of 10% in 5-year survival. Conclusion A substantial proportion of younger patients with AML have improved survival with the addition of GO to induction chemotherapy with little additional toxicity. J Clin Oncol 29: 369-377. (c) 2010 by American Society of Clinical Oncology

AB - Purpose Antibody-directed chemotherapy for acute myeloid leukemia (AML) may permit more treatment to be administered without escalating toxicity. Gemtuzumab ozogamicin (GO) is an immunoconjugate between CD33 and calicheamicin that is internalized when binding to the epitope. We previously established that it is feasible to combine GO with conventional chemotherapy. We now report a large randomized trial testing the addition of GO to induction and/or consolidation chemotherapy in untreated younger patients. Patients and Methods In this open-label trial, 1,113 patients, predominantly younger than age 60 years, were randomly assigned to receive a single dose of GO (3 mg/m(2)) on day 1 of induction course 1 with one of the following three induction schedules: daunorubicin and cytarabine; cytarabine, daunorubicin, and etoposide; or fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin. In remission, 948 patients were randomly assigned to GO in course 3 in combination with amsacrine, cytarabine, and etoposide or high-dose cytarabine. The primary end points were response rate and survival. Results The addition of GO was well tolerated with no significant increase in toxicity. There was no overall difference in response or survival in either induction of consolidation. However, a predefined analysis by cytogenetics showed highly significant interaction with induction GO (P = .001), with significant survival benefit for patients with favorable cytogenetics, no benefit for patients with poor-risk disease, and a trend for benefit in intermediate-risk patients. An internally validated prognostic index identified approximately 70% of patients with a predicted benefit of 10% in 5-year survival. Conclusion A substantial proportion of younger patients with AML have improved survival with the addition of GO to induction chemotherapy with little additional toxicity. J Clin Oncol 29: 369-377. (c) 2010 by American Society of Clinical Oncology

U2 - 10.1200/JCO.2010.31.4310

DO - 10.1200/JCO.2010.31.4310

M3 - Article

C2 - 21172891

VL - 29

SP - 369

EP - 377

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 4

ER -