Patients age 50-70 with previously untreated acute myeloid leukemia (AML) who are treated with Mylotarg® (gemtuzumab ozogamicin) plus standard chemotherapy appear to live longer than those who are treated with standard chemotherapy alone, according to the results of a study published in The Lancet.
Acute myeloid leukemia (AML) is a cancer of the bone marrow (spongy portion found in the middle of bones) and blood characterized by the rapid, uncontrolled growth of immature white blood cells known as myelocytes. The disease is more common in adults than in children; the average age at diagnosis is over 65.
There have been relatively large improvements in survival of younger patients with AML over the past two decades due to increased dose-intensity of therapy and stem cell transplants. However, there has been little, if any, improvement in the treatment of elderly patients with AML, often because elderly patients are not able to tolerate the more aggressive treatments used for younger patients. Treatment of elderly patients with AML remains unsatisfactory, and most patients die within a few months of diagnosis. One of the reasons for the dismal prognosis is the association with adverse cytogenetic and molecular abnormalities.
Mylotarg is a targeted agent that was originally approved in 2000 under the U.S. Food and Drug Administration’s (FDA) accelerate approval program; however, the confirmatory clinical trial required for full approval indicated that the drug did not improve survival and increased toxicity, including treatment-related death. Although the manufacturer (Pfizer, Inc.) voluntarily withdrew the drug from the market in 2010, clinical trials have continued.
The current trial involved 280 patients aged 50-70 years with previously untreated AML. The patients were randomized to receive either standard chemotherapy (with daunorubicin and cytrabine) or standard chemotherapy plus Mylotarg. In order to reduce side effects, the researchers used a low, fractionated dose of Mylotarg delivered over 3 days during chemotherapy (instead of a higher dose given over 2 days).
The researches found that adding a low, fractionated dose of Mylotarg to standard chemotherapy improved overall survival and event-free survival. After 2 years of follow-up, event-free survival was 41% for the patients in the Mylotarg/chemotherapy group compared to 17% for those in the chemotherapy group. Furthermore, the overall survival 2 years following treatment was 53% for patients who received Mylotarg compared to 42% for those who did not.
Patients in the Mylotarg group were more likely to experience side effects, including persistent reductions in white blood cells and platelets; however, the number of treatment-related deaths did not differ significantly between the two groups.
The researchers concluded that low fractionated-dose Mylotarg improves outcomes in patients with AML. As this runs directly counter to earlier studies that indicated that the drug was ineffective and too toxic, research will likely be ongoing.
Castaigne S, Pautas C, Terre C, et al. Effect of gemtuzumab ozogamicin on survival of adult patients with de-novo acute myeloid leukaemia (ALFA-0701): a randomised, open-label, phase 3 study. The Lancet. 2012; 379(9825): 1508-16.