Selective Ablation of Acute Myeloid Leukemia Using Antibody-Targeted Chemotherapy: A Phase I Study of an Anti-CD33 Calicheamicin Immunoconjugate

• Published in: Blood Vol. 93; no. 11; pp. 3678 - 3684
• Main Authors: Sievers, E.L., Appelbaum, F.R., Spielberger, R.T., Forman, S.J., Flowers, D., Smith, F.O., Shannon-Dorcy, K., Berger, M.S., Bernstein, I.D.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.06.1999
• Subjects: Adult; Aged; Aminoglycosides; Anti-Bacterial Agents - administration & dosage; Antibiotics, Antineoplastic - administration & dosage; Antibodies, Monoclonal - administration & dosage; Antigens, CD - immunology; Antigens, Differentiation, Myelomonocytic - immunology; Blood Cell Count - drug effects; Enediynes; Female; Hematopoiesis - drug effects; Humans; Immunoconjugates - administration & dosage; Immunoconjugates - immunology; Injections, Intravenous; Leukemia, Myeloid - drug therapy; Leukemia, Myeloid - immunology; Leukemia, Myeloid - physiopathology; Male; Middle Aged; Sialic Acid Binding Ig-like Lectin 3; Treatment Outcome
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V93.11.3678

Leukemic blast cells express the CD33 antigen in most patients with acute myeloid leukemia (AML), but this antigen is not expressed by hematopoietic stem cells. We conducted a study to determine whether normal hematopoiesis could be restored in patients with AML by selective ablation of cells expressing the CD33 antigen. In a dose escalation study, 40 patients with relapsed or refractory CD33+ AML were treated with an immunoconjugate (CMA-676) consisting of humanized anti-CD33 antibody linked to the potent antitumor antibiotic calicheamicin. The capacity of leukemic cells to efflux 3,3'-diethyloxacarbocyanine iodide (DiOC2) was used to estimate pretreatment functional drug resistance. Leukemia was eliminated from the blood and marrow of 8 (20%) of the 40 patients; blood counts returned to normal in three (8%) patients. A high rate of clinical response was observed in leukemias characterized by low dye efflux in vitro. Infusions of CMA-676 were generally well tolerated, and a postinfusion syndrome of fever and chills was the most common toxic effect. Two patients who were treated at the highest dose level (9 mg/m2) were neutropenic >5 weeks after the last dose of CMA-676. These results show that an immunoconjugate targeted to CD33 can selectively ablate malignant hematopoiesis in some patients with AML.