Gemtuzumab ozogamicin (brand name Mylotarg), is an antibody-drug conjugate used to treat acute myeloid leukemia. Gemtuzumab is a monoclonal antibody to CD33 linked to a cytotoxic agent from the class of calicheamicins. CD33 is expressed in most leukemic blast cells but also in normal hematopoietic cells, the intensity diminishing with maturation of stem cells.

Mylotarg Side Effects

The most common grade 3 and higher adverse reactions that occurred during Induction 1 and Intensification 2 in ≥ 5% of people who received gemtuzumab ozogamicin were infection, febrile neutropenia, decreased appetite, hyperglycemia, mucositis, hypoxia, hemorrhage, increased transaminase, diarrhea, nausea, and hypotension.

Gemtuzumab Ozogamicin Development

Gemtuzumab ozogamicin was created in a collaboration between Celltech and Wyeth that began in 1991. The same collaboration later produced inotuzumab ozogamicin. Celltech was acquired by UCB in 2004 and Wyeth was acquired by Pfizer in 2009.

In the United States, it was approved under an accelerated-approval process by the FDA in 2000, for use in patients over the age of 60 with relapsed acute myelogenous leukemia (AML); or those who are not considered candidates for standard chemotherapy. The accelerated approval was based on the surrogate endpoint of response rate. It was the first antibody-drug conjugate to be approved.

Within the first year after approval, the FDA required a black box warning be added to gemtuzumab packaging. The drug was noted to increase the risk of veno-occlusive disease (VOD) in the absence of bone marrow transplantation.

Later the onset of VOD was shown to occur at increased frequency in gemtuzumab patients even following bone marrow transplantation. The drug was discussed in a 2008 JAMA article, which criticized the inadequacy of postmarketing surveillance of biologic agents.

A randomized Phase III comparative controlled trial (SWOG S0106) was initiated in 2004, by Wyeth in accordance with the FDA accelerated-approval process. The study was stopped on August 20, 2009 prior to completion due to worrisome outcomes.

Among the patients evaluated for early toxicity, fatal toxicity rate was significantly higher in the gemtuzumab combination therapy group vs the standard therapy group. Mortality was 5.7% with gemtuzumab and 1.4% without the agent (16/283 = 5.7% vs 4/281 = 1.4%; P = .01).

In June 2010, Pfizer withdrew Mylotarg from the market at the request of the US FDA. However, some other regulatory authorities did not agree with the FDA decision, with Japan’s Pharmaceuticals and Medical Devices Agency stating in 2011 that the “risk-benefit balance of gemtuzumab ozogamicin has not changed from its state at the time of approval”.

In 2017, Pfizer reapplied for US and EU approval, based on a meta-analysis of prior trials and results of the ALFA-0701 clinical trial, an open-label Phase III trial in 280 older people with AML. In September 2017, gemtuzumab ozogamicin was approved again for use in the United States and in the European Union.


For future updates, subscribe via Newsletter here or Twitter