TY - JOUR
T1 - CD33 expression and its association with gemtuzumab ozogamicin response
T2 - Results from the randomized phase III children's oncology group trial AAML0531
AU - Pollard, Jessica A.
AU - Loken, Michael
AU - Gerbing, Robert B.
AU - Raimondi, Susana C.
AU - Hirsch, Betsy A.
AU - Aplenc, Richard
AU - Bernstein, Irwin D.
AU - Gamis, Alan S.
AU - Alonzo, Todd A.
AU - Meshinchi, Soheil
N1 - Publisher Copyright:
© 2016 American Society of Clinical Oncology. All rights reserved.
PY - 2016/3/1
Y1 - 2016/3/1
N2 - Purpose CD33 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 CD33 expression level. Patients and Methods CD33 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. Results Patients with low CD33 expression (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 CD33 expression (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 (HR) patients with low CD33 expression had similar outcomes regardless of GO exposure, whereas the addition of GO to conventional chemotherapy resulted in a significant decrease in RR and disease-free survival (DFS) for patients with higher CD33 expression (LR RR, GO 13% v No-GO 35%, P = .001; LR DFS, GO 79% v No-GO 59%, P = .007; IR RR, GO 44% v No-GO 57%, P = .044; IR DFS, GO 51% v No-GO 40%, P = .078; HR RR, GO 40% v No-GO 73%, P = .016; HR DFS, GO 47% v No-GO 28%, P = .135). Conclusion We demonstrate that GO lacks clinical benefit in patients with low CD33 expression but significantly reduces RR and improves EFS in patients with high CD33 expression, which suggests a role for CD33-targeted therapeutics in subsets of pediatric AML.
AB - Purpose CD33 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 CD33 expression level. Patients and Methods CD33 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. Results Patients with low CD33 expression (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 CD33 expression (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 (HR) patients with low CD33 expression had similar outcomes regardless of GO exposure, whereas the addition of GO to conventional chemotherapy resulted in a significant decrease in RR and disease-free survival (DFS) for patients with higher CD33 expression (LR RR, GO 13% v No-GO 35%, P = .001; LR DFS, GO 79% v No-GO 59%, P = .007; IR RR, GO 44% v No-GO 57%, P = .044; IR DFS, GO 51% v No-GO 40%, P = .078; HR RR, GO 40% v No-GO 73%, P = .016; HR DFS, GO 47% v No-GO 28%, P = .135). Conclusion We demonstrate that GO lacks clinical benefit in patients with low CD33 expression but significantly reduces RR and improves EFS in patients with high CD33 expression, which suggests a role for CD33-targeted therapeutics in subsets of pediatric AML.
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U2 - 10.1200/JCO.2015.62.6846
DO - 10.1200/JCO.2015.62.6846
M3 - Article
C2 - 26786921
AN - SCOPUS:84964294715
SN - 0732-183X
VL - 34
SP - 747
EP - 755
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 7
ER -