CD33 Expression and Its Association With Gemtuzumab Ozogamicin Response: Results From the Randomized Phase III Children's Oncology Group Trial AAML0531.

PurposeCD33 is variably expressed on acute myeloid leukemia (AML) blasts and is targeted by gemtuzumab ozogamicin(GO). GO has shown benefit in both adult and pediatric AML trials, yet limited data exist about whether GO response correlates with CD33expression level.Patients and MethodsCD33 expression levels were prospectively quantified by multidimensional flow cytometry in 825 patients enrolled in Children’s Oncology Group AAML0531 and correlated with response to GO.ResultsPatients with low CD33expression (lowest quartile of expression [Q1]) had no benefit with the addition of GO to conventional chemotherapy (relapse risk [RR]: GO 36% v No-GO 34%, P = .731; event-free survival [EFS]: GO 53% v No-GO 58%, P = .456). However, patients with higher CD33expression (Q2 to Q4) had significantly reduced RR (GO 32% v No-GO 49%, P < .001) and improved EFS (GO 53% v No-GO 41%, P = .005). This differential effect was observed in all risk groups. Specifically, low-risk (LR), intermediate-risk (IR), and high-risk (...