Delivery of Calicheamicin via New Antibody Is Promising in AML

ASCO--Treatment with an investigational immunoconjugate, CMA-676, safelyinduced remissions in some patients with refractory or relapsed acute myelogenousleukemia (AML), Eric L. Sievers, MD, said in his poster presentation ofthe preliminary results at the American Society of Clinical Oncology annualmeeting.

The immunoconjugate consists of a potent cytotoxic agent, calicheamicin,linked to a recombinant engineered human antibody directed against theCD33 antigen, which is expressed on a high percentage of AML blast cells.

"The lack of CD33 antigen expression on hematopoietic stem cellsallows for selective delivery of the cytotoxic agent to the tumor target,while sparing normal stem cells," Dr. Sievers said. All patients inthe trial had CD33-positive disease. The compound is being codevelopedby 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 MedicalCenter, Duarte, Calif, CMA-676 was delivered via a two-hour IV infusiononce every 14 days for up to three courses of treatment. The highest dosetested was 9 mg/m².

The agent was well-tolerated, with fever and chills the most commonside 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 studyachieved complete remission of their disease for approximately six months.In addition, seven patients experienced morphologic remission (no morphologicevidence of leukemia identified in the bone marrow).