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

TitleCD33 Expression and Its Association With Gemtuzumab Ozogamicin Response: Results From the Randomized Phase III Children's Oncology Group Trial AAML0531.
Publication TypeJournal Article
Year of Publication2016
AuthorsPollard JA, Loken MR, Gerbing RB, Raimondi SC, Hirsch BA, Aplenc R, Bernstein ID, Gamis AS, Alonzo TA, Meshinchi S
JournalJ Clin Oncol
Volume34
Issue7
Pagination747-55
Date Published2016 Mar 1
ISSN1527-7755
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.

DOI10.1200/JCO.2015.62.6846
Alternate JournalJ. Clin. Oncol.
PubMed ID26786921