CD33_PGx6_Score Predicts Gemtuzumab Ozogamicin Response in Childhood Acute Myeloid Leukemia: A Report From the Children’s Oncology Group

Chauhan L, Shin M, Wang YC, Loken M, Pollard J, Aplenc R, Hirsch BA, Raimondi S, Ries RE, Bernstein ID, Gamis AS, Alonzo TA, Meshinchi S, Lamba JK. CD33_PGx6_Score Predicts Gemtuzumab Ozogamicin Response in Childhood Acute Myeloid Leukemia: A Report From the Children’s Oncology Group. JCO Precis Oncol. 2019;3. doi: 10.1200/PO.18.00387. eCollection 2019. PubMed PMID: 32914031; PubMed Central PMCID: PMC7446480.

The US Food and Drug Administration recently announced reapproval of gemtuzumab ozogamicin (GO) for treatment of CD33-positive acute myeloid leukemia (AML), thus opening up opportunities to develop strategies for effective use of GO. In light of our recent report showing prognostic significance of CD33 splicing single nucleotide polymorphisms (SNPs), the objective of this study was to comprehensively evaluate CD33 SNPs for accurate prediction of patients with AML who are more or less likely to respond to GO. We investigated the five new CD33 SNPs (rs2455069, rs35112940, rs61736475, rs1803254, and rs201074739) for association with CD33 leukemic cell surface expression and clinical response in pediatric patients with AML enrolled in the Children’s Oncology Group AAML0531 trial. We further developed a composite CD33 pharmacogenetics (PGx) score using six CD33 SNPs (CD33_PGx6_score) for association with clinical outcome.