Journal
JOURNAL OF CLINICAL ONCOLOGY
Volume 39, Issue 3, Pages 215-+Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1200/JCO.20.01892
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Funding
- Band of Parents
- Kids Walk for Kids with Cancer
- Cycle for Survival
- Arms Wide Open Childhood Cancer Foundation
- Cookies for Kids' Cancer
- End Kids Cancer
- Press On Foundation
- National Cancer Institute [P30 CA008748]
- MSK's Clinical Grade Production Facility for vaccine production
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The study investigated the kinetics of antibody response to GD2/GD3 vaccine and beta-glucan in HR-NB patients, showing that higher anti-GD2-IgG1 titer was associated with improved survival.
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 beta-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% +/- 66%, and the overall survival (OS) was 71% +/- 67% at 5 years. Serum anti-GD2 (immunoglobulin G1 [IgG1] and IgM) and anti-GD3 (IgG1) titers showed notable increases following the initiation of beta-glucan at week 6. There was an association between IgG1 titer and SNP rs3901533 of dectin-1, the beta-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 beta-glucan elicited robust antibody responses in patients with HR-NB with prior PD. Higher anti-GD2-IgG1 titer was associated with improved survival. (C) 2020 by American Society of Clinical Oncology
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