Originally published as JCO Early Release 10.1200/JCO.2005.04.6011 on May 8 2006

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FCGR2A Polymorphism Is Correlated With Clinical Outcome After Immunotherapy of Neuroblastoma With Anti-GD2 Antibody and Granulocyte Macrophage Colony-Stimulating Factor

Nai-Kong V. Cheung, Rebecca Sowers, Andrew J. Vickers, Irene Y. Cheung, Brian H. Kushner, Richard Gorlick

From the Departments of Pediatrics and Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center; and the Department of Pediatrics, Children's Hospital at Montefiore, Albert Einstein College of Medicine, New York, NY

Address reprint requests to Nai-Kong V. Cheung, MD, PhD, Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY 10021; e-mail: cheungn{at}mskcc.org

PURPOSE: Anti-GD2 murine IgG3 antibody 3F8 kills neuroblastoma cells by antibody-dependent cell-mediated cytotoxicity (ADCC). Granulocyte macrophage colony-stimulating factor (GM-CSF) enhances phagocyte-mediated ADCC. The differential affinity of the human FCGR polymorphic alleles for 3F8 may influence the effectiveness of antibody immunotherapy.

PATIENTS AND METHODS: The entire cohort of high risk neuroblastoma patients (N = 136) treated on protocol using 3F8 and GM-CSF were the subjects of this analysis. Tumor response was measured by standard clinical tools plus sensitive molecular monitoring using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Polymorphic alleles of FCGR2A and FCGR3A were determined by PCR plus direct sequencing using genomic DNA samples obtained from marrow or blood of patients.

RESULTS: FCGR2A (R/R) genotype correlated with progression-free survival for the entire cohort (P = .049) and for the subset of patients with no history of prior relapse (P = .023). FCGR2A (R/R) also correlated with marrow remission 2.5 months after treatment initiation: by histology (P = .021 and P = .036, for the entire cohort and the subset, respectively) and by qRT-PCR (P = .052 and P = .033, respectively).

CONCLUSION: The favorable outcome associated with FCGR2A (R/R) genotype is consistent with the proposed role of FCGR2A and phagocyte-mediated ADCC in 3F8 plus GM-CSF immunotherapy.

Supported by in part by Grants No. CA106450 and CA095742 from the National Institutes of Health, and by grants from the Robert Steel Foundation, Pediatric Cancer Foundation, The Aubrey Fund, Margaux's Miracle Foundation, Hope Street Kids, and Katie-Find-A-Cure Fund.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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