Gemtuzumab ozogamicin for the treatment of acute promyelocytic leukemia: mechanisms of action and resistance, safety and efficacy.

Abstract

INTRODUCTION:

Acute promyelocytic leukemia (APL) is characterized by peculiar biological features and high sensitivity to therapeutic agents such as anthracyclines, all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). Because cure rates of up to 80 - 90% have been reported using various combinations of the above agents, future strategies will probably aim at reducing therapy-related toxicity while maintaining therapeutic efficacy. Gemtuzumab ozogamicin (GO) is a calicheamicin-conjugated mAb directed against CD33, a surface antigen highly expressed on APL blasts. GO has been shown to be effective in this disease and better tolerated than conventional chemotherapy.

AREAS COVERED:

This review looks at the mechanism of action, pathways associated with resistance and toxicity profile of GO. Reported experience on the use of GO for relapsed or newly diagnosed APL is also discussed along with evidence on its efficacy and relative tolerability in APL management. In addition to its activity in advanced disease, data suggest that GO in various combinations may replace chemotherapy in APL front-line therapy. This should apply in particular to some subsets such as elderly patients or those unfit to receive conventional chemotherapy.

EXPERT OPINION:

GO has proven effective and relatively safe as a single agent in advanced APL. In combinations with ATRA and/or ATO, GO may substitute for conventional chemotherapy of APL, particularly in unfit patients.

• Authors: Massimo Breccia, Francesco Lo-Coco
• Journal: Expert opinion on biological therapy (Expert Opin Biol Ther) Vol. 11 Issue 2 Pg. 225-34 (Feb 2011) ISSN: 1744-7682 [Electronic] England
• PMID: 21142804 (Publication Type: Journal Article, Review)

Chemical References

• Aminoglycosides
• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Antineoplastic Agents
• gemtuzumab

Topics

• Aminoglycosides (pharmacology)
• Antibodies, Monoclonal (pharmacology)
• Antibodies, Monoclonal, Humanized
• Antineoplastic Agents (pharmacology)
• Clinical Trials as Topic
• Drug Resistance, Neoplasm
• Humans
• Leukemia, Promyelocytic, Acute (drug therapy)
• Safety
• Treatment Outcome