Adding gemtuzumab ozogamicin (GO) to standard chemotherapy improved outcomes in children with KMT2A-rearranged acute myeloid leukemia (AML), according to a study published in the Journal of Clinical Oncology.

Pediatric patients with KMT2A-rearranged AML typically express higher levels of CD33, a characteristic associated with poor prognosis. Researchers sought to determine if adding GO, an anti-CD33 monoclonal antibody, to conventional chemotherapy would confer survival benefits for patients with KMT2A-rearranged AML.

The researchers evaluated patients from the phase 3 Children’s Oncology Group AAML0531 trial ( Identifier: NCT01407757). Patients in this trial were randomly assigned to receive standard chemotherapy with GO or chemotherapy alone. Of the entire cohort, 215 patients had KMT2A-rearranged AML.

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GO significantly improved event-free survival (EFS), but not overall survival (OS), in KMT2A-rearranged AML. The 5-year EFS rate was 48% with GO and 29% without it (P =.003). The 5-year OS rate was 63% and 53%, respectively (P =.054).

Among patients who achieved a complete remission, those who received GO had a lower relapse rate and superior 5-year disease-free survival (DFS). The relapse rate was 40% in patients who received GO and 66% in those who did not (P =.001). The 5-year DFS rate was 57% and 33%, respectively (P =.002).

The benefits associated with GO were observed in both high-risk and low-risk KMT2A-rearranged subsets. Although the response to GO was affected by the level of CD33 expression, patients with lower CD33 expression also benefited from GO.

Prior GO treatment in hematopoietic stem cell transplant (HSCT) recipients was associated with a decrease in relapse rate. The 5-year relapse rate was 28% in patients who received GO before HSCT, compared with 73% in patients who underwent HSCT with no prior GO treatment (P =.006).

“GO in combination with hematopoietic stem cell transplant may provide additive clinical benefit; however, this needs to be studied further prospectively,” the study authors wrote.

In a multivariable analysis, GO was independently associated with a lower rate of relapse and improved EFS and DFS.

Overall, GO was associated with significant improvements in long-term clinical outcomes for patients with KMT2A-rearranged AML, the study authors concluded.

“Treatment of KMT2A-r AML should include the CD33-targeting agent GO; future trials should study second-generation CD33-targeting agents and further define the role of hematopoietic stem cell transplant in this disease subset,” the authors wrote.

Disclosures: This research was supported by the Children’s Oncology Group and the National Cancer Institute. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Pollard J, Guest E, Alonzo TA, et al. Gemtuzumab Ozogamicin Improves Event-Free Survival and Reduces Relapse in Pediatric KMT2A-Rearranged AML: Results From the Phase III Children’s Oncology Group Trial AAML0531. J Clin Oncol. Published online May 28, 2021. doi:10.1200/JCO.20.03048