Anti-GD2 Antibody with GM-CSF, Interleukin-2, and Isotretinoin for NeuroblastomaPédiatrie - Publié le 05/01/2020 par Ilfad Blazevic
Preclinical and preliminary clinical data indicate that ch14.18, a monoclonal antibody against the tumor-associated disialoganglioside GD2, has activity against neuroblastoma and that such activity is enhanced when ch14.18 is combined with
granulocyte–macrophage colony-stimulating factor (GM-CSF) or interleukin-2. We
conducted a study to determine whether adding ch14.18, GM-CSF, and interleukin-2
to standard isotretinoin therapy after intensive multimodal therapy would improve
outcomes in high-risk neuroblastoma.
Patients with high-risk neuroblastoma who had a response to induction therapy and
stem-cell transplantation were randomly assigned, in a 1:1 ratio, to receive standard
therapy (six cycles of isotretinoin) or immunotherapy (six cycles of isotretinoin and
five concomitant cycles of ch14.18 in combination with alternating GM-CSF and interleukin-2). Event-free survival and overall survival were compared between the immunotherapy group and the standard-therapy group, on an intention-to-treat basis.
A total of 226 eligible patients were randomly assigned to a treatment group. In the
immunotherapy group, a total of 52% of patients had pain of grade 3, 4, or 5, and
23% and 25% of patients had capillary leak syndrome and hypersensitivity reactions, respectively. With 61% of the number of expected events observed, the study
met the criteria for early stopping owing to efficacy. The median duration of followup was 2.1 years. Immunotherapy was superior to standard therapy with regard to
rates of event-free survival (66±5% vs. 46±5% at 2 years, P=0.01) and overall survival
(86±4% vs. 75±5% at 2 years, P=0.02 without adjustment for interim analyses).
Immunotherapy with ch14.18, GM-CSF, and interleukin-2 was associated with a
significantly improved outcome as compared with standard therapy in patients
with high-risk neuroblastoma. (Funded by the National Institutes of Health and
the Food and Drug Administration; ClinicalTrials.gov number, NCT00026312.)
Source : NEJM, 2010