Treatment of acute promyelocytic leukemia with gemtuzumab ozogamicin.
Acute promyelocytic leukemia (APL) is a form of acute myeloid leukemia characterized by peculiar biologic features and a unique sensitivity to differentiation therapy with all-trans retinoic acid (ATRA). Modern treatment approaches to APL include simultaneous combination of ATRA and anthracycline-based chemotherapy. Gemtuzumab ozogamicin is a calicheamicin-conjugated monoclonal antibody directed against CD33, a cell surface antigen highly expressed on APL cells. Engagement of CD33 by gemtuzumab results in immunoconjugate internalization and hydrolytic release of calicheamicin, which, in turn, causes irreversible DNA damage and cell death. A number of preliminary reports have highlighted the sensitivity of APL to gemtuzumab given alone or in combination with other agents. Several reasons may account for the efficacy of gemtuzumab in APL, including: (1) CD33 is detectable in virtually 100% of APL cases; (2) calicheamicin belongs to the anthracycline family, a group of chemotherapeutic agents known to be highly effective in APL; and (3) the APL blast cells lack the multidrug resistance glycoprotein 170. Due to the availability of other highly effective agents (ATRA, arsenic trioxide), relatively few APL patients have been treated thus far with gemtuzumab, and their follow-up is still short. However, it is conceivable that the use of this agent in APL will increase in the near future in light of its capability to induce molecular remission even in advanced disease. Furthermore, the use of low doses of gemtuzumab in high-risk patients might be relevant in order to reduce treatment toxicity due to conventional anthracyclines. This review summarizes the mechanism of action and toxicity profile of gemtuzumab as well as the published experience with this compound in patients with newly diagnosed and relapsed APL.
Department of Biopathology, University of Tor Vergata, Rome, Italy. lo.coco@uniroma2.it
Francesco
F
Lo Coco
Emanuele
E
Ammatuna
Nélida
N
Noguera
D000617:Aminoglycosides / Q000378:metabolism / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000378:metabolism / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000627:therapeutic use; D005260:Female; D000079982:Gemtuzumab; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D010087:Oxides / Q000627:therapeutic use
D000617:Aminoglycosides; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D001152:Arsenicals; D010087:Oxides; D000079982:Gemtuzumab; D000077237:Arsenic Trioxide