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J Clin Oncol. 2016 Mar 1;34(7):747-55. doi: 10.1200/JCO.2015.62.6846. Epub 2016 Jan 19.

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

Author information

1
Jessica A. Pollard, Maine Medical Center, Portland, ME; and Tufts University, Boston, MA; Michael Loken, Hematologics; Irwin D. Bernstein and Soheil Meshinchi, Fred Hutchinson Cancer Research Center; Irwin D. Bernstein and Soheil Meshinchi, University of Washington, Seattle, WA; Robert B. Gerbing and Todd A. Alonzo, Children's Oncology Group, Arcadia; Todd A. Alonzo, Keck School of Medicine of University of Southern California, Los Angeles, CA; Susana C. Raimondi, St Jude Children's Research Hospital, Memphis, TN; Betsy Hirsch, University of Minnesota Cancer Center, Minneapolis, MN; Richard Aplenc, Children's Hospital of Philadelphia, Philadelphia, PA; and Alan S. Gamis, Children's Mercy Hospitals and Clinics, Kansas City, MO. jpollard@mmc.org.
2
Jessica A. Pollard, Maine Medical Center, Portland, ME; and Tufts University, Boston, MA; Michael Loken, Hematologics; Irwin D. Bernstein and Soheil Meshinchi, Fred Hutchinson Cancer Research Center; Irwin D. Bernstein and Soheil Meshinchi, University of Washington, Seattle, WA; Robert B. Gerbing and Todd A. Alonzo, Children's Oncology Group, Arcadia; Todd A. Alonzo, Keck School of Medicine of University of Southern California, Los Angeles, CA; Susana C. Raimondi, St Jude Children's Research Hospital, Memphis, TN; Betsy Hirsch, University of Minnesota Cancer Center, Minneapolis, MN; Richard Aplenc, Children's Hospital of Philadelphia, Philadelphia, PA; and Alan S. Gamis, Children's Mercy Hospitals and Clinics, Kansas City, MO.

Abstract

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.

PMID:
26786921
PMCID:
PMC4872025
DOI:
10.1200/JCO.2015.62.6846
[Indexed for MEDLINE]
Free PMC Article

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