In a single-institution phase II study reported in the Journal of Clinical Oncology, Cheung et al found that a subcutaneous ganglioside G2/G3 vaccine plus oral β-glucan produced antibody responses in patients with high-risk neuroblastoma, with higher anti–GD2-IgG1 titers being associated with improved survival.

As stated by the investigators, “Anti-GD2 monoclonal antibody has proven efficacy in high-risk neuroblastoma. A small phase I GD2/GD3 vaccine trial described long-term survival and a favorable safety profile among patients with a history of disease progression. The kinetics of mounting antibody response to vaccine and its prognostic impact on survival are now investigated in a phase II study.”

Study Details

The study included 102 patients, enrolled between December 2012 and September 2018 at Memorial Sloan Kettering Cancer Center, who had achieved remission after salvage therapies. Patients had a history of one (63%), two (21%), or three to six (16%) episodes of disease progression, with 82% experiencing disease progression after anti-GD2 monoclonal antibody therapy (m3F8/dinutuximab/naxitamab). Age at diagnosis was < 18 months for 7% and ≥ 18 months for 93%. The median time from diagnosis to the first disease progression was 23.8 months.

Patients received seven subcutaneous injections of GD2/GD3 vaccine (each containing 30 µg of GD2 and 30 µg of GD3) over 1 year at weeks 1, 2, 3, 8, 20, 32, and 52, plus oral β-glucan at 40 mg/kg/d for 14 days on/14 days off starting at week 6 for a total of 13 planned cycles. Median time from last disease progression to vaccination was 13.0 months.

Key Findings

Median follow-up was 3.4 years (range = 0.4­–7.3 years). Progression-free survival at 6 months, 2 years, and 5 years from initiation of vaccine treatment was 76.5%, 45.3%, and 32.2%. Overall survival at these time points was 99%, 88.4%, and 70.7%.

Serum anti-GD2 IgG1 and IgM and anti-GD3 IgG1 exhibited marked increases following initiation of β-glucan at week 6. Significant associations of anti-GD2 (P = .020) and anti-GD3 (P = .042) IgG1 titers, but not IgM titers, were observed with presence of the single nucleotide polymorphism rs3901533 in dectin-1, the β-glucan receptor.

On multivariate analysis, anti–GD2-IgG1 titer ≥150 ng/mL (3rd quartile) by week 8 was associated with significantly better progression-free survival (hazard ratio [HR] = 0.37, P = .007) and overall survival (HR = 0.13, P = .04) vs titer < 150 ng/mL. Having more than one prior episode of disease progression was associated with poorer progression-free survival vs one prior episode (HR = 1.79, P = .03). Time from last disease progression of ≥ 12 months vs < 12 months was associated with better progression-free survival (HR = 0.54, P = .02).

Vaccine-related toxicities were self-limited injection-associated local reactions, including grade 1 or 2 pain and fever, with no grade ≥ 3 toxicities being observed. No treatment-related serious adverse events, hospitalizations, neuropathy, neuropathic pain, ophthalmoplegia, capillary leak syndrome, or long-term toxicities were reported.

The investigators concluded, “GD2/GD3 vaccine plus β-glucan elicited robust antibody responses in patients with high-risk neuroblastoma with prior disease progression. Higher anti–GD2-IgG1 titer was associated with improved survival.”

Irene Y. Cheung, ScD, of Memorial Sloan Kettering Cancer Center, Department of Pediatrics, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by the 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, and National Cancer Institute. For full disclosures of the study authors, visit ascopubs.org.