Although the five year survival rate of children with high risk neuroblastoma have increased
over the last three decades from 4 to 44 % (1), neuroblastoma is the second most frequent
cause for cancer related death in childhood (11 %). Most patients show good initial response
rates (complete (CR) and partial remission (PR) rate 95 %), but 55 % experience a largely
treatment-resistant tumor progression.
Recently, a breakthrough with immunotherapy was reported by US investigators from the
Children's Oncology Group (2) using the anti-ganglioside D2 (GD2) monoclonal antibody ch14.18
for tumor cell destruction and granulocyte macrophage-colony stimulating factor (GM-CSF) plus
interleukin 2 (IL-2) for immunostimulation. This immune therapy resulted in an increase of 20
% Event free survival (EFS) at 2 year from randomization. However, this was associated with a
high toxicity rate (pain, capillary leak syndrome).
The proposed trial compares the Childrens' Oncology Group (COG) "standard of care" arm
(anti-GD2 + GM-CSF + IL-2 i.v. + retinoic acid oral) with an experimental arm (anti-GD2 +
GM-CSF + IL-2 s.c. + retinoic acid oral) designed to reduce toxicity.
The potential benefit from this trial consists of the confirmation that the American trial
design is feasible in an independent set of patients with different preceding therapy, at a
different time point regarding to immune reconstitution after autologous stem cell
transplantation (ASCT), the feasibility of a newly designed immunotherapy (which is hopefully
less toxic) and the investigation of immune response parameters. This pilot study is the
prerequisite for a consecutive randomized clinical trial comparing two immunotherapeutic
approaches in a larger set of patients.