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Genetic and Proteomic Advances Pave the Way for Next-Generation Leukemia Therapies
Date:12/10/2011

aggressive leukemia that can be fatal within weeks to months of diagnosis without proper treatment. However, with the recent development of targeted therapies, additional research has focused on improving patient outcomes while reducing toxicity associated with conventional chemotherapy regimens. Monoclonal antibodies, or MABs, attach to the cancer cell surface and, when conjugated to a toxin, release the toxin into the cell. MABs are a relatively new type of targeted therapy and are considered an enhancement to chemotherapy that allows treatment to target specific cells while reducing the toxicity to healthy cells. Because GO binds to CD33, an antigen present on AML cells, but not to normal hematopoietic stem cells, it has been the focus of recent research because of its ability to be directed specifically to AML cells.

To evaluate the efficacy of GO when used with chemotherapy in older AML patients, a team of researchers with the Acute Leukemia French Association designed a Phase III, prospective, open-label, randomized trial. Primary study endpoints focused on event-free survival (EFS); secondary endpoints included response rate, disease-free survival (DFS), overall survival (OS), and safety over a three-year follow-up period. Study participants (adults age 50-70 with previously untreated de novo, or first occurrence of, AML) were randomized into one of two treatment arms – either standard chemotherapy referred to as DA, (daunorubicin, ara-C, n=134) or chemotherapy with the addition of GO (DAGO, n=137). 

The study demonstrated that adding GO to a standard chemotherapy regimen significantly improved EFS and OS in older adult AML patients. At two years of follow-up, the rate of EFS was estimated at 15.6 percent in the DA arm compared with 41.4 percent in the DAGO arm. DFS was estimated at 18.1 percent in the DA arm versus 48.5 percent in the DAGO arm. The benefit in EFS was observed in all age groups and translated into a longer OS
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SOURCE American Society of Hematology
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