Treatment of 11q23/MLL + AML with Gemtuzumab Ozogamicin: Results from the Randomized Phase III Children's Oncology Group Trial AAML0531

CD33 is variably expressed on acute myeloid leukemia (AML) blasts and is the target of gemtuzumab ozogamicin (GO). We previously demonstrated the clinical benefit of GO treatment in children with AML treated on COG AAML0531 in which patients were randomized to receive standard Medical Research Council-based chemotherapy with or without GO. We also demonstrated that CD33 expression is highly variable in pediatric AML and that children with 11q23 translocations involving the KMT2A gene, previously known as the mixed lineage leukemia gene and referred to here as MLL+, have significantly higher CD33 expression, as defined by mean fluorescent intensity (MFI) values, than patients without 11q23/MLL + leukemia (MLL-) [median CD33 MFI: MLL + 229.13 (range 6-1351) vs. MLL-129 (range 2.68-1225.87) P <0.001.] Given significantly elevated levels of CD33 expression in MLL + AML and our previous findings showing an association between high CD33 expression and improved response to GO, we evaluated MLL + AML patients treated on COG AAML0531 to determine whether GO treatment improved their clinical outcomes.