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Clinical Trial
. 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

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Free PMC article
Clinical Trial

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

Jessica A Pollard et al. J Clin Oncol. .
Free PMC article

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.

Conflict of interest statement

Authors’ disclosures of potential conflicts of interest are found in the article online at www.jco.org. Author contributions are found at the end of this article.

Figures

Fig 1.
Fig 1.
Distribution of CD33 expression in patients. (A) Correlation of CD33 expression data with specific cytogenetic/molecular disease characteristics by quartile. (B) CD33 expression and disease risk group classification by quartile. CBF, core-binding factor; FLT3/ITD, FLT3 internal tandem duplication.
Fig 2.
Fig 2.
Association of CD33 levels and GO response. (A) Event-free survival from study entry for patients with low CD33 expression levels (Q1) when analyzed by treatment arm. (B) Event-free survival from study entry for patients with higher CD33 expression levels (Q2 to Q4) when analyzed by treatment arm. (C) Relapse risk from complete remission for patients with low CD33 expression levels (Q1) when analyzed by treatment arm. (D) Relapse risk from complete remission for patients with higher CD33 expression levels (Q2 to Q4) when analyzed by treatment arm. GO, gemtuzumab ozogamicin; Q, quartile.
Fig 3.
Fig 3.
Association of CD33 levels and GO response by treatment arm and risk group. Relapse risk from complete remission by treatment arm. (A) Low-risk patients with low CD33 expression (Q1). (B) Low-risk patients with high CD33 expression (Q2 to Q4). (C) Intermediate-risk patients with low CD33 expression (Q1). (D) Intermediate-risk patients with high CD33 expression (Q2 to Q4). (E) High-risk patients with low CD33 expression (Q1). (F) High-risk patients with high CD33 expression (Q2 to Q4). GO, gemtuzumab ozogamicin; Q, quartile.
Fig A1.
Fig A1.
Association of CD33 levels and GO response by treatment arm (GO v No-GO) and consolidation therapy (HSCT v chemotherapy) for patients with (A) low (Q1) CD33 expression and (B) higher (Q2to Q4) CD33 expression. Chemo, chemotherapy; GO, gemtuzumab ozogamicin; HSCT, hematopoietic stem cell transplantation; Q, quartile.
Fig A2.
Fig A2.
Disease-free survival by quartile and treatment arm (GO v No-GO) for (A) Q1, (B) Q2, (C) Q3, and (D) Q4. Chemo, chemotherapy; GO, gemtuzumab ozogamicin; HSCT, hematopoietic stem cell transplantation; Q, quartile.

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