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Delivery of Calicheamicin via New Antibody Is Promising in AML

Delivery of Calicheamicin via New Antibody Is Promising in AML

ASCO--Treatment with an investigational immunoconjugate, CMA-676, safely induced remissions in some patients with refractory or relapsed acute myelogenous leukemia (AML), Eric L. Sievers, MD, said in his poster presentation of the preliminary results at the American Society of Clinical Oncology annual meeting.

The immunoconjugate consists of a potent cytotoxic agent, calicheamicin, linked to a recombinant engineered human antibody directed against the CD33 antigen, which is expressed on a high percentage of AML blast cells.

"The lack of CD33 antigen expression on hematopoietic stem cells allows for selective delivery of the cytotoxic agent to the tumor target, while sparing normal stem cells," Dr. Sievers said. All patients in the trial had CD33-positive disease. The compound is being codeveloped by the Fred Hutchinson Cancer Research Center, Seattle, Celltech PLC (UK), and Wyeth-Ayerst Research.

In this phase I dose-escalation trial, conducted at the Hutchinson Center, where Dr. Sievers is affiliated, and the City of Hope National Medical Center, Duarte, Calif, CMA-676 was delivered via a two-hour IV infusion once every 14 days for up to three courses of treatment. The highest dose tested was 9 mg/m².

The agent was well-tolerated, with fever and chills the most common side effects. Some degree of liver toxicity was observed in three patients, but no dose-limiting toxicity was seen. Two of the 39 patients in the study achieved complete remission of their disease for approximately six months. In addition, seven patients experienced morphologic remission (no morphologic evidence of leukemia identified in the bone marrow).

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