Survival impact of anti-GD2 antibody response in a phase II ganglioside vaccine trial among patients with high-risk neuroblastoma with prior disease progression Journal Article


Authors: Cheung, I. Y.; Cheung, N. K. V.; Modak, S.; Mauguen, A.; Feng, Y.; Basu, E.; Roberts, S. S.; Ragupathi, G.; Kushner, B. H.
Article Title: Survival impact of anti-GD2 antibody response in a phase II ganglioside vaccine trial among patients with high-risk neuroblastoma with prior disease progression
Abstract: PURPOSE: Anti-GD2 monoclonal antibody (mAb) has proven efficacy in high-risk neuroblastoma (HR-NB). A small phase I GD2/GD3 vaccine trial (n = 15) described long-term survival and a favorable safety profile among patients with a history of disease progression (PD). The kinetics of mounting antibody response to vaccine and its prognostic impact on survival are now investigated in a phase II study (ClinicalTrials.gov identifier: NCT00911560). PATIENTS AND METHODS: One hundred two patients with HR-NB who achieved remission after salvage therapies were enrolled in this trial. They received seven subcutaneous injections of GD2/GD3 vaccine spanning 1 year plus oral β-glucan starting at week 6 after the third dose of vaccine. Serum anti-vaccine antibody titers were quantified by enzyme-linked immunosorbent assay. Single nucleotide polymorphisms (SNPs) were determined by quantitative polymerase chain reaction. Kaplan-Meier and landmark Cox Regression models were used for survival estimates. RESULTS: Patients had a history of one (63%), two (21%), or three to six (16%) episodes of PD. 82% of them progressed following anti-GD2 mAb (m3F8/dinutuximab/naxitamab) therapy. Vaccine-related toxicities were self-limited injection-associated local reactions and fever without any > grade 3 toxicities. The progression-free survival (PFS) was 32% ± 6%, and the overall survival (OS) was 71% ± 7% at 5 years. Serum anti-GD2 (immunoglobulin G1 [IgG1] and IgM) and anti-GD3 (IgG1) titers showed notable increases following the initiation of β-glucan at week 6. There was an association between IgG1 titer and SNP rs3901533 of dectin-1, the β-glucan receptor. Multivariable analyses showed that anti-GD2-IgG1 titer ≥ 150 ng/mL by week 8 was associated with favorable PFS and OS, while having prior episodes of PD and the time from last PD to vaccine were associated with PFS. CONCLUSION: GD2/GD3 vaccine plus β-glucan elicited robust antibody responses in patients with HR-NB with prior PD. Higher anti-GD2-IgG1 titer was associated with improved survival.
Journal Title: Journal of Clinical Oncology
Volume: 39
Issue: 3
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2021-01-20
Start Page: 215
End Page: 226
Language: English
DOI: 10.1200/jco.20.01892
PUBMED: 33326254
PROVIDER: scopus
DOI/URL:
Notes: Article -- Export Date: 1 March 2021 -- Source: Scopus
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Citation Impact
MSK Authors
  1. Brian Kushner
    260 Kushner
  2. Nai-Kong Cheung
    569 Cheung
  3. Shakeel Modak
    201 Modak
  4. Govindaswami Ragupathi
    138 Ragupathi
  5. Irene Y Cheung
    84 Cheung
  6. Ellen Marlese Basu
    69 Basu
  7. Stephen Stacy Roberts
    80 Roberts
  8. Yi Feng
    9 Feng
  9. Audrey   Mauguen
    62 Mauguen