Murine anti-GD2 monoclonal antibody 3F8 combined with granulocyte- macrophage colony-stimulating factor and 13-cis-retinoic acid in high-risk patients with stage 4 neuroblastoma in first remission Journal Article


Authors: Cheung, N. K. V.; Cheung, I. Y.; Kushner, B. H.; Ostrovnaya, I.; Chamberlain, E.; Kramer, K.; Modak, S.
Article Title: Murine anti-GD2 monoclonal antibody 3F8 combined with granulocyte- macrophage colony-stimulating factor and 13-cis-retinoic acid in high-risk patients with stage 4 neuroblastoma in first remission
Abstract: Purpose: Anti-GD2 monoclonal antibody (MoAb) combined with granulocyte-macrophage colony-stimulating factor (GM-CSF) has shown efficacy against neuroblastoma (NB). Prognostic variables that could influence clinical outcome were explored. Patients and Methods: One hundred sixty-nine children diagnosed with stage 4 NB (1988 to 2008) were enrolled onto consecutive anti-GD2 murine MoAb 3F8 ± GM-CSF ± 13-cis-retinoic acid (CRA) protocols after achieving first remission (complete remission/very good partial remission). Patients enrolled in regimen A (n = 43 high-risk [HR] patients) received 3F8 alone; regimen B (n = 41 HR patients), 3F8 + intravenous GM-CSF + CRA, after stem-cell transplantation (SCT); and regimen C (n = 85), 3F8 + subcutaneous GM-CSF + CRA, 46 of 85 after SCT, whereas 28 of 85 required additional induction therapy and were deemed ultra high risk (UHR). Marrow minimal residual disease (MRD) was measured by quantitative reverse transcription polymerase chain reaction. Survival probability was calculated by the Kaplan-Meier method, and prognostic variables were analyzed by multivariate Cox regression model. Results: At 5 years from the start of immunotherapy, progression-free survival (PFS) improved from 44% for HR patients receiving regimen A to 56% and 62% for those receiving regimens B and C, respectively. Overall survival (OS) was 49%, 61%, and 81%, respectively. PFS and OS of UHR patients were 36% and 75%, respectively. Relapse was mostly at isolated sites. Independent adverse prognostic factors included UHR (PFS) and post-cycle two MRD (PFS and OS), whereas the prognostic factors for improved outcome were missing killer immunoglobulin-like receptor ligand (PFS and OS), human antimouse antibody response (OS), and regimen C (OS). Conclusion: Retrospective analysis of consecutive trials from a single center demonstrated that MoAb 3F8 + GM-CSF + CRA is effective against chemotherapy-resistant marrow MRD. Its positive impact on long-term survival can only be confirmed definitively by randomized studies. © 2012 by American Society of Clinical Oncology.
Keywords: child; preschool child; school child; disease-free survival; unclassified drug; major clinical study; cancer recurrence; cancer patient; cancer staging; progression free survival; reverse transcription polymerase chain reaction; multiple cycle treatment; pain; antineoplastic combined chemotherapy protocols; stem cell transplantation; high risk patient; monoclonal antibody; cancer regression; antibodies, monoclonal; proportional hazards model; immunotherapy; immunoglobulin g; infant; neuroblastoma; minimal residual disease; erythema; remission induction; kaplan meier method; isotretinoin; drug dose increase; recombinant granulocyte macrophage colony stimulating factor; urticaria; monoclonal antibody 3f8; granulocyte-macrophage colony-stimulating factor
Journal Title: Journal of Clinical Oncology
Volume: 30
Issue: 26
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2012-09-10
Start Page: 3264
End Page: 3270
Language: English
DOI: 10.1200/jco.2011.41.3807
PROVIDER: scopus
PMCID: PMC3434986
PUBMED: 22869886
DOI/URL:
Notes: --- - "Export Date: 2 November 2012" - "CODEN: JCOND" - "Source: Scopus"
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MSK Authors
  1. Brian Kushner
    186 Kushner
  2. Nai-Kong Cheung
    430 Cheung
  3. Kim Kramer
    165 Kramer
  4. Shakeel Modak
    156 Modak
  5. Irene Y Cheung
    72 Cheung