Gemtuzumab Ozogamicin in AML: Reconsideration May Be Merited

Recent reports on the benefit of gemtuzumab ozogamicin (Mylotarg, Pfizer/Wyeth) for patients with acute myeloid leukemia have led to calls for the drug to be returned to the market, but questions have been raised about the data.

In June 2010, gemtuzumab ozogamicin was voluntarily withdrawn from the market in the United States by the manufacturer. The drug had been granted accelerated approval by the US Food and Drug Administration (FDA) in 2000, but a confirmatory trial (SWOG SO106) and years of postmarketing experience "have not shown evidence of clinical benefit in patients with AML," the FDA reported at the time of the withdrawal.

Since then, however, 2 separate investigator-led clinical trials have reported beneficial results with gemtuzumab ozogamicin. This has created quite a buzz among hematologists treating leukemia patients and has led to calls to return the drug to the market.

The AML16 Trial, headed by Alan Burnett, MD, from the Cardiff University School of Medicine in the United Kingdom (J Clin Oncol. 2012;30:3924-3931), found a trend toward improvement in survival.

The ALFA 0701 trial headed by Sylvie Castaigne, MD, from Hôpital de Versailles in France (Lancet. 2012,379:1508-1516), found a significant improvement in survival. Dr. Castaigne and colleagues conclude "that our results support the reevaluation of the place of gemtuzumab ozogamicin in available front-line therapy for acute myeloid leukemia."

However, FDA officials do not seem to be convinced. In a letter published online March 25 in the Journal of Clinical Oncology, they discuss limitations in the subset analyses in both of these studies, and conclude that "the publications of AML16 and ALFA 0701 currently do not provide clarity with regard to the statistical analysis plan and these limitations."

The FDA is committed to examining the totality of data from all trials, the officials note. In the meantime, although gemtuzumab ozogamicin has been withdrawn from the market in the United States, the drug is available to patients through access programs.

"I concur that there seem to be shortcomings in the reporting of each of these studies," writes Donna Neuberg, MD, from the Dana-Farber Cancer Institute in Boston, Massachusetts, in response to that letter. "I continue to believe that the 2 reports, taken together, may merit reconsideration for [gemtuzumab ozogamicin]," she notes.

However, Dr. Neuberg adds that "without a broad and complete assessment of all the data, I cannot say whether that would lead to approval."

Dr. Neuberg has disclosed no relevant financial relationships.

J Clin Oncol. Published online March 25, 2013. Letter, Reply