Antibody-Targeted Chemotherapy Fights AML With Fewer Side Effects
At the 35th Annual Meeting of the American Society of Clinical Oncology (ASCO), researchers presented new data on the use of a pioneering drug technology known as "antibody-targeted chemotherapy" to fight acute myelogenous leukemia (AML), a virulent and often fatal form of cancer. In a clinical study, the experimental agent, CMA-676, induced 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 replace normal bone marrow and blood cells. It is one of 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 good as well as bad cells—patients receiving standard chemotherapy tend to become very ill. Researchers at the Fred Hutchinson Cancer Research Center (Seattle), in collaboration with scientists from thirteen leading leukemia centers—including University of Chicago Medical Center (Chicago), MD Anderson Cancer Center (Houston), and the University of Pennsylvania Cancer Center (Philadelphia)—are working with Wyeth-Ayerst Research (Radnor, PA) and Celltech (Slough, UK) 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. However, the cell surface molecule is absent from normal blood stem cells, the seeds from which normal blood and immune cells originate. Specially engineered to carry a novel and extremely potent chemotherapy agent known as calicheamicin, the antibody selectively targets leukemic blast cells, while sparing cells that replenish normal blood cells once the leukemia is eradicated.
Results from a pivotal Phase II trial, involving patients who experienced a relapse following initial AML chemotherapy, are promising. CMA-676 administered alone appears to produce remission among 36% of patients, which is comparable to the effectiveness of standard combination chemotherapy regimens. The data also indicate that CMA-676 has several important advantages over standard agents.
Standard combination chemotherapy treatment often produces significant major organ damage and sores both in the mouth and 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.
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