Gemtuzumab ozogamicin reduces relapse risk in FLT3/ITD acute myeloid leukemia: a report from the Children's Oncology Group.

Publication Type:

Journal Article

Source:

Clinical cancer research : an official journal of the American Association for Cancer Research (2015)

Abstract:

PURPOSE: Gemtuzumab ozogamicin (GO), a calicheamicin-conjugated monoclonal antibody 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 2 consecutive Children's Oncology Group (COG) 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 vs. No-GO cohorts were identical (64% vs. 64%; p=0.98). Relapse rate (RR) after initial CR was 37% for GO recipients vs. 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% vs. 40% (p=0.079), 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.