Open Access
Review

Antibody-based therapy of acute myeloid leukemia with gemtuzumab ozogamicin

Andrew J. Cowan1,George S. Laszlo2,Elihu H. Estey2,3, Roland B. Walter2,3,4,*
1
Hematology/Oncology Fellowship Program, University of Washington, Seattle, WA, USA
2
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
3
Department of Medicine, Division of Hematology, University of Washington, Seattle, WA, USA
4
Department of Epidemiology, University of Washington, Seattle, WA, USA
DOI: 10.2741/4181 Volume 18 Issue 4, pp.1311-1334
Published: 01 June 2013
(This article belongs to the Special Issue Clinical antibody drug conjugates)
*Corresponding Author(s):  
Roland B. Walter
E-mail:  
rwalter@fhcrc.org
Abstract

Antibodies have created high expectations for effective yet tolerated therapeutics in acute myeloid leukemia (AML). Hitherto the most exploited target is CD33, a myeloid differentiation antigen found on AML blasts in most patients and, perhaps, leukemic stem cells in some. Treatment efforts have focused on conjugated antibodies, particularly gemtuzumab ozogamicin (GO), an anti-CD33 antibody carrying a toxic calicheamicin-γ1 derivative that, after intracellular hydrolytic release, induces DNA strand breaks, apoptosis, and cell death. Serving as paradigm for this strategy, GO was the first anti-cancer immunoconjugate to obtain regulatory approval in the U.S. While efficacious as monotherapy in acute promyelocytic leukemia (APL), GO alone induces remissions in less than 25- 35% of non-APL AML patients. However, emerging data from well controlled trials now indicate that GO improves survival for many non-APL AML patients, supporting the conclusion that CD33 is a clinically relevant target for some disease subsets. It is thus unfortunate that GO has become unavailable in many parts of the world, and the drug’s usefulness should be reconsidered and selected patients granted access to this immunoconjugate.

Key words

AML, Antibody, Calicheamicin, CD33, Gemtuzumab ozogamicin, Immunoconjugate, Review

Share and Cite
Andrew J. Cowan, George S. Laszlo, Elihu H. Estey, Roland B. Walter. Antibody-based therapy of acute myeloid leukemia with gemtuzumab ozogamicin. Frontiers in Bioscience-Landmark. 2013. 18(4); 1311-1334.