Antibody-targeted chemotherapy with CMA-676 uses breakthrough technology to treat leukemia

December 06, 1999

Fred Hutchinson Cancer Research Center Researchers Present Updated Study Results at the American Society of Hematology Meeting in New Orleans

NEW ORLEANS, DEC. 7, 1999 - Today, at the 41st Annual Meeting and Exposition of the American Society of Hematology (ASH), scientists presented the latest data on the use of a pioneering drug technology known as "antibody-targeted chemotherapy" to fight acute myeloid leukemia (AML) - a virulent and often fatal form of cancer. The experimental agent, CMA-676, induces remission in a significant proportion of patients with few serious side effects. CMA-676 represents the first successful application of antibody-targeted chemotherapy.

AML is an aggressive, life-threatening disease in which certain white blood cells become cancerous and rapidly accumulate in the bone marrow, preventing normal marrow from growing and functioning properly. AML is among the most serious forms of adult leukemia, with a relatively high fatality rate. Most patients require intensive chemotherapy to achieve complete remission, and some also must undergo bone marrow transplants. Up to half of patients with AML, even after such intensive treatment, have residual leukemic cells or experience a relapse.

Because current chemotherapy drugs to treat AML are non-specific - destroying normal as well as malignant cells - patients receiving standard chemotherapy tend to become very sick. Researchers at the Fred Hutchinson Cancer Research Center, in collaboration with scientists from eleven leading leukemia centers, including University of Chicago Medical Center, MD Anderson Cancer Center, and The University of Pennsylvania Cancer Center, are working with Wyeth-Ayerst Research and Celltech Chiroscience PLC to study CMA-676, an antibody-drug conjugate that delivers treatment directly to the leukemia cells.

The specificity of the conjugate lies in the antibody, which recognizes a cell-surface molecule that is abundant on AML cells. Importantly, however, the cell surface molecule is absent from normal blood stem cells, the seeds from which normal blood and immune cells originate. This engineered antibody specifically carries a novel and extremely potent chemotherapy agent known as calicheamicin, the antibody selectively targets leukemic blast cells, while sparing cells that are responsible for replenishing normal blood cells once the leukemia is eradicated.

Promising results continue to emerge from a pivotal Phase II trial in the U.S., which involves patients who experienced a relapse following initial AML chemotherapy. CMA-676 given alone produces remission among 34 percent of patients - a rate comparable to that of standard combination chemotherapy regimens. The data also indicate that CMA-676 has several important advantages over standard agents.

"CMA-676 provides continuous suppression of AML with mild and well-tolerated side effects for many patients," said Eric Sievers, M.D., of Fred Hutchinson Cancer Research Center. "The side effects associated with this antibody-targeted chemotherapy appear to be less severe than those commonly associated with standard chemotherapy."

Whereas standard combination chemotherapy treatment often produces significant major organ damage, and sores both in the mouth and in the intestinal tract (frequent sources for opportunistic infections), CMA-676 treatment does not. CMA-676 also is associated with a relatively low treatment-related mortality. As with standard chemotherapy treatments, CMA-676 produces a temporary suppression of bone marrow and blood cell counts.

CMA-676 is administered in two IV infusions fourteen days apart, and many patients have received the drug on an outpatient basis. Unlike standard chemotherapy regimens, which involve multiple drugs, CMA-676 is given alone.

Similar studies of this new therapy are underway throughout Europe and Canada, and the developers of CMA-676 eventually hope to adapt their groundbreaking technology for the treatment of other devastating cancers.
The Fred Hutchinson Cancer Research Center is an independent, non-profit research institution dedicated to the development and advancement of biomedical technology to eliminate cancer and other potentially fatal diseases. Recognized internationally for its pioneering work in bone marrow transplantation, the Center has four scientific divisions collaborating to form a unique environment for conducting basic and applied science. One of 35 National Cancer Institute-designated comprehensive cancer centers in the country, it is the only one in the Northwest. Visit the Hutchinson Center web site for more information at .

Advancing knowledge, saving lives

For information about Wyeth-Ayerst Laboratories, contact: Douglas Petkus, 610/971-4980.

Fred Hutchinson Cancer Research Center

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