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.

Advances in Lipid-Based Nanoparticles for Cancer Chemoimmunotherapy

“…IFN-α, including IFN-α-2a and IFN-α-2b (Intron A ® and Sylatron ® ), was approved for subsets of patients with leukemia, sarcoma, lymphoma, and melanoma [48][49][50][51]. In 2020, a new cytokine, GM-CSF, combined with naxitamab-gqgk (Danyelza), a targeted antibody against the GD-2 pathway, was approved for the treatment of relapsed/refractory neuroblastoma in the bone or bone marrow [52]. The clinical use of these cytokines marked a milestone in cancer immunotherapy.…”

Naxitamab combined with granulocyte‐macrophage colony‐stimulating factor as consolidation for high‐risk neuroblastoma patients in complete remission

“…Whether an anti‐idiotype network is generated with all anti‐GD2 antibodies is currently unknown and needs further investigation. Recently published experience of a large cohort of second and further CR HR‐NB patients treated with bivalent GD2/GD3 vaccine and oral beta‐glucans has shown 5‐year EFS of 32% and OS of 71% 33 . In this study, the natural anti‐GD2 titers released by the vaccine were associated with outcome.…”

Novel Treatments and Technologies Applied to the Cure of Neuroblastoma

“…Cheung et al [41] recently published the results of a phase II trial for a bivalent vaccine with escalating doses of the immunological adjuvant OPT-821, combined with oral β-glucan. The patient cohort was composed of 102 patients with high-risk NB in remission.…”