Gemtuzumab ozogamicin in acute myeloid leukemia: a remarkable saga about an active drug.

Despite living in an era of unprecedented progress in the understanding of the genetic and molecular biology of acute myeloid leukemia (AML), this has not translated into significant advances in therapy. Never before have so many potential targets been studied. Yet most have not advanced beyond the phase 1 and, occasionally, phase 2 studies. The few ongoing phase 3 studies seem unlikely to have more than a marginal benefit, if at all. Thus, it is not surprising that in past few decades almost no new drugs for AML have received regulatory approval. In 2000, gemtuzumab ozogamicin (GO) was granted accelerated approval by the US Food and Drug Administration based on promising phase 2 data in relapsed older adults with AML. GO held promise as a new agent that also could be efficacious in newly diagnosed AML with acceptable toxicity. Several phase 3 studies were designed to test GO in this setting. The results of a randomized study by the Southwest Oncology Group led in 2010 to the voluntary withdrawal of this agent when improved efficacy could not be demonstrated and toxicity appeared excessive. Since then, 4 randomized studies have been completed that, in aggregate, strongly support the efficacy of this agent in newly diagnosed AML with acceptable toxicity. There is a very plausible explanation for this discrepancy, making a compelling case for reapproval of GO in AML.