Gemtuzumab Ozogamicin Reduces Relapse Risk in FLT3/ITD Acute Myeloid Leukemia: A Report from the Children's Oncology Group.

TitleGemtuzumab Ozogamicin Reduces Relapse Risk in FLT3/ITD Acute Myeloid Leukemia: A Report from the Children's Oncology Group.
Publication TypeJournal Article
Year of Publication2015
AuthorsTarlock K, Alonzo TA, Gerbing RB, Raimondi SC, Hirsch BA, Sung L, Pollard JA, Aplenc R, Loken MR, Gamis AS, Meshinchi S
JournalClin Cancer Res
Date Published2015 Dec 7
ISSN1078-0432
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 with FLT3/ITD.

EXPERIMENTAL DESIGN: We analyzed children with FLT3/ITD-positive AML (n = 183) treated on two consecutive Children's Oncology Group AML trials (NCT00070174 and NCT00372593). Outcomes were assessed for FLT3/ITD patients receiving standard chemotherapy with or without GO (GO vs. No-GO, respectively), and the impact of consolidation HCT for high-risk FLT3/ITD patients [high FLT3/ITD allelic ratio (ITD-AR)].

RESULTS: For all FLT3/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-risk FLT3/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).

CONCLUSIONS: CD33 targeting with HCT consolidation may be an important therapeutic strategy in high-risk FLT3/ITD AML and its efficacy and associated toxicity warrant further investigation. Clin Cancer Res; 1-7. ©2015 AACR.

DOI10.1158/1078-0432.CCR-15-1349
Alternate JournalClin. Cancer Res.
PubMed ID26644412
Grant ListU10 CA098413 / CA / NCI NIH HHS / United States
U10 CA098543 / CA / NCI NIH HHS / United States
U10 CA180886 / CA / NCI NIH HHS / United States