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Gemtuzumab Ozogamicin Reduces Relapse Risk in FLT3/ITD Acute Myeloid Leukemia: A Report from the Children's Oncology Group.
- Source :
-
Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2016 Apr 15; Vol. 22 (8), pp. 1951-7. Date of Electronic Publication: 2015 Dec 07. - Publication Year :
- 2016
-
Abstract
- Purpose: Gemtuzumab ozogamicin (GO), a calicheamicin-conjugated mAb against CD33, has been used in the treatment of acute myeloid leukemia (AML). We evaluated the impact of the addition of GO to standard chemotherapy and hematopoietic stem cell transplant (HCT) in patients withFLT3/ITD.<br />Experimental Design: We analyzed children withFLT3/ITD-positive AML (n= 183) treated on two consecutive Children's Oncology Group AML trials (NCT00070174andNCT00372593). Outcomes were assessed forFLT3/ITD patients receiving standard chemotherapy with or without GO (GO vs. No-GO, respectively), and the impact of consolidation HCT for high-riskFLT3/ITD patients [highFLT3/ITD allelic ratio (ITD-AR)].<br />Results: For allFLT3/ITD patients, complete remission (CR) rates for the GO versus No-GO cohorts were identical (64% vs. 64%;P= 0.98). Relapse rate (RR) after initial CR was 37% for GO recipients versus 59% for No-GO recipients (P= 0.02), disease-free survival (DFS) was similar (47% vs. 41%;P= 0.45), with higher treatment-related mortality (TRM) in GO recipients (16% vs. 0%;P= 0.008). Among high-riskFLT3/ITD patients with high ITD-AR, those who received HCT in first CR with prior exposure to GO had a significant reduction in RR (15% vs. 53%;P= 0.007), with a corresponding DFS of 65% versus 40% (P= 0.08), and higher TRM (19% vs. 7%;P= 0.08).<br />Conclusions: CD33 targeting with HCT consolidation may be an important therapeutic strategy in high-riskFLT3/ITD AML and its efficacy and associated toxicity warrant further investigation.<br /> (©2015 American Association for Cancer Research.)
- Subjects :
- Adolescent
Adult
Child
Child, Preschool
Female
Follow-Up Studies
Gemtuzumab
Hematopoietic Stem Cell Transplantation
Humans
Infant
Infant, Newborn
Leukemia, Myeloid, Acute diagnosis
Leukemia, Myeloid, Acute mortality
Male
Prognosis
Recurrence
Treatment Outcome
Young Adult
Aminoglycosides therapeutic use
Antibodies, Monoclonal, Humanized therapeutic use
Antineoplastic Agents therapeutic use
Gene Duplication
Leukemia, Myeloid, Acute drug therapy
Leukemia, Myeloid, Acute genetics
fms-Like Tyrosine Kinase 3 genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1557-3265
- Volume :
- 22
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Clinical cancer research : an official journal of the American Association for Cancer Research
- Publication Type :
- Academic Journal
- Accession number :
- 26644412
- Full Text :
- https://doi.org/10.1158/1078-0432.CCR-15-1349