13.05.2018 kl 23:59 501

Abstract SIDE 116

Phase II Trial of GD2-KLH/GD3-KLH Vaccine for Stage 4 Neuroblastoma In
𕟴nd Remission: Induced Anti-GD2 Titer Strongly Correlates with Survival

Memorial Sloan Kettering Cancer Center, New York, United States

Background: Anti-GD2 antibodies mouse 3F8 and hu3F8 have proven survival benefit in patients with high
risk stage 4 neuroblastoma (HR-NB). Both antibodies induced de novo anti-GD2 antibody response. A Phase
I vaccine trial utilizing GD2-keyhole limpet hemocyanin (KLH)/GD3-KLH in 15 patients found no dose-limiting
toxicities (Kushner et al., CCR 2014).

Methods: In this Phase II trial, 7 doses of 60ug of GD2-KLH/GD3-KLH conjugate vaccine mixed with 150ug of
adjuvant OPT821 were administered subcutaneously in outpatient setting over one year in 84 patients with
HR-NB in 𕟴nd remission oral yeast beta-glucan at 40mg/kg/day x 2 weeks q month x 10 months was
included to enhance antibody mediated cytotoxicity. Progression-free survival (PFS) and overall survival (OS)
were estimated by Kaplan Meier analyses.

Results: All 84 patients had prior relapse, 57 treated in 2nd remission, 18 in 3rd remission, and the rest in
4th to 7th remission. All had prior exposure to either mouse 3F8 (63%), and/or hu3F8 (57%), and/or
dinutuximab (46%). Median follow-up was 16 months PFS was 51%±7% and OS were 90%±5% at 2 years
with no ≥grade 3 toxicities. Serum anti-GD2 and anti-GD3 IgG1 antibodies were measured using ELISA at
serial time points, integrated, and expressed as area-under-the-curve per month. Anti-GD2 titer was
positive pre-vaccine in 14% of patients (median=39ng/ml), and positive post-vaccine in 78% (median=134
ng/mL/month). Developing anti-GD2 antibody titer did not result in any patient having pain or neuropathy.
There was no correlation between pre-vaccine and post-vaccine titer. Anti-GD2 antibody titer
>134ng/ml/month was prognostic for improved PFS and OS (p=0.033 and 0.025, respectively). In contrast,
developing anti-GD3 response had no prognostic significance for survival. There was no impact on patient
outcome based on age at diagnosis, time from diagnosis, MYCN amplification, number of prior relapses, prevaccine
anti-GD2 antibody therapy, as well as pre-vaccine anti-GD2 serum titer.

Conclusion: These results confirmed the safety of GD2-KLH/GD3-KLH vaccine and the potential influence of
anti-GD2 but not anti-GD3 seroconversion on PFS and OS. If the 90% OS is confirmed in a phase III randomized trial, GD2 vaccine could provide a viable option to improve the outlook for patients with relapsed HR-NB