Despite major research advances over the last several decades that have helped deliver improved therapeutic options for leukemia, the condition remains deadly. Specialists are in need of new options to help diagnose the condition earlier and new therapies that will extend patients' lives. New research addressing important updates on the diagnosis and treatment of leukemia were presented at the 53rd Annual Meeting of the American Society of Hematology.

"While recent discoveries during the past several decades have paved the way for a much better understanding of how the proteins affecting cancer cells can determine response or resistance to treatment, more progress needs to be made," said Martin S. Tallman, M.D., moderator of the press conference and Chief of the Leukemia Service at Memorial Sloan-Kettering Cancer Center in New York. "The abstracts discussed today represent important steps toward targeting these proteins with effective therapies that will make a meaningful difference in the lives of leukemia patients."

A phase III clinical trial of monoclonal antibody gemtuzumab ozogamicin (GO) finds that the investigational therapy may be a promising option when used in relatively low, frequently repeated doses in conjunction with standard chemotherapy to treat older adults with acute myeloid leukemia (AML) according to researchers.

Chemotherapy has long been the standard of care for induction in patients with AML, an 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 (19 months vs. 34 months on average in DA arm vs. DAGO arm).

The treatment protocol had some toxicity, as the rate of fatal adverse events possibly attributable to treatment was 6.7 percent in the DA group and 8.7 percent in the DAGO group. Prolonged grade 3 or greater thrombocytopenia was observed in 19 DAGO patients, and three episodes of veno-occlusive disease or sinusoidal obstructive syndrome were observed in the DAGO arm, two noted as fatal. There were no differences between the arms in the incidence of severe sepsis or in the rate of intensive care unit admission during the course of therapy.

"Research has demonstrated that GO has very potent anti-cancer properties, and with this study we have identified a dosing regimen that gives patients the therapeutic benefit without some of the toxicities previously reported at higher doses," said lead author Sylvie Castaigne, M.D., Professor in the Department of Hematology at Hopital de Versailles in Versailles, France. "Specialists treating AML have not been offered a new therapeutic option for several decades, and with this research we are encouraged that GO may be able to deliver better overall outcomes for these AML patients with limited.