TY - JOUR
T1 - Gemtuzumab ozogamicin for the treatment of acute promyelocytic leukemia
T2 - Mechanisms of action and resistance, safety and efficacy
AU - Breccia, Massimo
AU - Lo-Coco, Francesco
PY - 2011/2
Y1 - 2011/2
N2 - 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.
AB - 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.
KW - acute promyelocytic leukemia
KW - efficacy
KW - gentuzumab ozogamicin
KW - safety
UR - http://www.scopus.com/inward/record.url?scp=78651378808&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=78651378808&partnerID=8YFLogxK
U2 - 10.1517/14712598.2011.543895
DO - 10.1517/14712598.2011.543895
M3 - Article
C2 - 21142804
AN - SCOPUS:78651378808
VL - 11
SP - 225
EP - 234
JO - Expert Opinion on Biological Therapy
JF - Expert Opinion on Biological Therapy
SN - 1471-2598
IS - 2
ER -