For Older Patients with Leukemia, Low Doses of Gemtuzumab Improve SurvivalIn a randomized trial, patients aged 50 to 70 with previously untreated acute myeloid leukemia (AML) who received the targeted therapy gemtuzumab ozogamicin (Mylotarg) in addition to standard chemotherapy lived longer than patients who received standard chemotherapy alone. These results, published online in The Lancet on April 4, counter some earlier studies that indicated that the drug was ineffective and too toxic.
Gemtuzumab received accelerated approval for AML from the Food and Drug Administration (FDA) in 2000, but the confirmatory clinical trial required for full approval showed that the drug did not improve survival and increased toxicity, including the risk of treatment-related death. The manufacturer, Pfizer Inc., voluntarily withdrew the drug from the general market in 2010, though clinical trials have continued.
In the current trial, which was conducted by the Acute Leukemia French Association, the researchers used a lower dose given over 3 days during chemotherapy instead of a higher dose given over 2 days to reduce side effects. In the study, 139 patients received standard chemotherapy with the drugs daunorubicin and cytarabine, and 139 received standard chemotherapy plus gemtuzumab ozogamicin.
The addition of low, fractionated doses of gemtuzumab ozogamicin improved overall survival and event-free survival (time to relapse, death, or assessment that the disease is not responding to treatment). After 2 years of follow-up, event-free survival was 41 percent for the patients who received gemtuzumab ozogamicin and 17 percent in the control group. Overall survival 2 years after treatment was 53 percent in the gemtuzumab ozogamicin group and 42 percent in the control group.
Although patients in the gemtuzumab ozogamicin group were more likely to experience side effects, particularly more-persistent reductions in white blood cells and platelets, deaths during treatment did not differ significantly between the two groups. “The use of fractionated lower doses of gemtuzumab ozogamicin allows the safe delivery of higher cumulative doses and substantially improves outcomes in patients with acute myeloid leukemia,” wrote the authors.
“These results are quite important if confirmed [in additional trials],” commented Dr. Wyndham Wilson of NCI’s Center for Cancer Research, who was not involved in the research. Few advances have been made in the treatment of older patients with AML in recent years, he added, and effective new drugs are badly needed.