The role of gemtuzumab ozogamicin in acute leukaemia therapy.
Gemtuzumab ozogamicin (GO) is an immunoconjugate that binds to CD33 on the surface of acute myeloid leukaemia (AML) blasts and, after internalisation, releases a cytotoxic drug, calicheamicin. GO is approved by the US Food and Drug Administration for the treatment of CD33-positive AML at first relapse in patients 60 years and older who are not candidates for other cytotoxic therapy. GO as a single agent has low antileukaemic activity. When given to patients meeting the criteria noted above, it produces a complete response (CR) rate of only 12%, with another 12% achieving CR with inadequate platelet recovery (CRp). The median survival of patients treated with GO monotherapy is 11.2 months. GO therapy at 9 mg/m(2) is complicated with hepatic veno-occlusive disease in 5-10% of patients, particularly prior to or following stem cell transplantation. GO at lower doses combined with chemotherapy as induction or postremission therapy is promising, however, and phase III trials are ongoing. GO is probably most active in acute promyelocytic leukaemia (APL). It is used for induction regimens in high-risk APL and for the elimination of minimal residual APL. Case reports suggest that GO also has activity in CD33-positive acute lymphoblastic leukaemia. In conclusion, single agent GO can induce responses in patients with CD33-positive AML in first recurrence. The future of GO is its use in combination with other cytotoxic agents. Ongoing clinical trials may better define the role of GO combinations, particularly in untreated AML.
Tsimberidou
Apostolia-Maria
AM
Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA. atsimber@mdanderson.org
Giles
Francis J
FJ
Estey
Elihu
E
O'Brien
Susan
S
Keating
Michael J
MJ
Kantarjian
Hagop M
HM
D000208:Acute Disease; D000617:Aminoglycosides / Q000008:administration & dosage* / Q000378:metabolism / Q000627:therapeutic use*; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000378:metabolism / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D004351:Drug Resistance; D053281:Enediynes; D000079982:Gemtuzumab; D006801:Humans; D000922:Immunotoxins / Q000378:metabolism / Q000627:therapeutic use*; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000378:metabolism; D011485:Protein Binding; D016032:Randomized Controlled Trials as Topic; D012008:Recurrence; D063268:Sialic Acid Binding Ig-like Lectin 3
D000617:Aminoglycosides; D000903:Antibiotics, Antineoplastic; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; C571163:CD33 protein, human; D053281:Enediynes; D000922:Immunotoxins; D063268:Sialic Acid Binding Ig-like Lectin 3; C055955:calicheamicin gamma(1)I; D000079982:Gemtuzumab