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Blood, Vol. 93 No. 11 (June 1), 1999:
pp. 3678-3684
Selective Ablation of Acute Myeloid Leukemia Using Antibody-Targeted
Chemotherapy: A Phase I Study of an Anti-CD33 Calicheamicin
Immunoconjugate
E.L. Sievers,
F.R. Appelbaum,
R.T. Spielberger,
S.J. Forman,
D. Flowers,
F.O. Smith,
K. Shannon-Dorcy,
M.S. Berger, and
I.D. Bernstein
From the Clinical Research Division, Fred Hutchinson Cancer Research
Center, Seattle; the Departments of Pediatrics and Medicine, University
of Washington, Seattle, WA; the Department of Hematology and Bone
Marrow Transplantation, City of Hope National Medical Center, Duarte,
CA; and Wyeth Ayerst Research, Radnor, PA.
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.
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