Reviewing the benefits of gemtuzumab ozogamicin in different patients with acute myeloid leukemia

This review aimed to explore the effectiveness and safety of gemtuzumab ozogamicin (GO; Mylotarg) in different subtypes of acute myeloid leukemia (AML).  

This review concluded that this treatment is safe and effective in certain patients with AML.  

GO is an anti-CD33 antibody-drug conjugate that has been used in previous trials for the treatment of AML. It is composed of 2 parts: a monoclonal antibody (gemtuzumab) and a chemotherapy drug (ozogamicin). Most AML cells have on their surface a protein called CD33. Gemtuzumab targets the CD33 protein on leukemia cells. It then releases the drug ozogamicin into the leukemia cells to damage and kill them.  

GO was the first antibody-conjugate drug approved by the FDA. However, it was then withdrawn due to risks of blood clotting at high doses. Later studies have shown that these risks were lower at lower doses of GO when added to chemotherapy regimens, with benefits on the survival of patients with AML. Also, there are many categories of patients with AML, based on age, gender, genetic abnormalities of AML, which can influence the effect of the drug. It is important to evaluate the risks and benefits of GO across different subgroups of AML patients.  

This review involved data from 30 studies that evaluated the safety and effectiveness of GO in AML. Overall, 11,234 patients were included. 4,678 patients were treated with GO and 6,466 patients received non-GO therapies.

Overall, the rate of complete responses (CR; complete disappearance of cancer) was similar between the GO (73.32%) and the non-GO (64.52%) groups. However, a significantly improved overall survival (by 14%) was seen in the GO group compared to the non-GO group. 

This survival benefit was seen across different karyotypes (a collection of chromosomes that contain the genetic material of an individual). GO advantages were associated with nucleophosmin 1 mutations (NPM1), wild-type FMS-like tyrosine kinase 3 internal tandem duplication gene (FLT-ID3), age greater than 70 years, de novo AML (not secondary to another blood cancer), and presence of CD33 on AML cells.  

Adding GO into induction therapy improved survival, as did a lower dose (lower than 6mg/m²) of GO.  

GO was related to an increased risk of early death at a higher dose (of 6mg/m² or higher) compared to non-GO therapies. Liver-related side effects, and higher risk for blocked blood vessels in the liver, particularly at high doses. There was no difference in other side effects such as infections between the 2 groups. 

This review concluded that GO treatment at a lower dose and early in the treatment is safe and effective in certain patients with AML such as those younger than 70 years, those with high CD33 expression, and those with NPM1 mutation, or without FLT3-ITD mutation.

This study analyzed very different studies, with different protocols. The patients included and therapy combination were very different. More studies are needed.