title: Anti-GD2 antibody with GM-CSF, interleukin-2, and isotretinoin for neuroblastoma.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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 follow-up 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).
  
  
  CONCLUSIONS
  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.)
authors.affiliation: University of California, San Diego, and Moores Cancer Center, San Diego, CA 92103-8447, USA. aliceyu@ucsd.edu
authors.forename: Alice L
authors.initials: AL
authors.lastname: Yu
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Gilman
authors.forename: M Fevzi
authors.initials: MF
authors.lastname: Ozkaynak
authors.forename: Wendy B
authors.initials: WB
authors.lastname: London
authors.forename: Susan G
authors.initials: SG
authors.lastname: Kreissman
authors.forename: Helen X
authors.initials: HX
authors.lastname: Chen
authors.forename: Malcolm
authors.initials: M
authors.lastname: Smith
authors.forename: Barry
authors.initials: B
authors.lastname: Anderson
authors.forename: Judith G
authors.initials: JG
authors.lastname: Villablanca
authors.forename: Katherine K
authors.initials: KK
authors.lastname: Matthay
authors.forename: Hiro
authors.initials: H
authors.lastname: Shimada
authors.forename: Stephan A
authors.initials: SA
authors.lastname: Grupp
authors.forename: Robert
authors.initials: R
authors.lastname: Seeger
authors.forename: C Patrick
authors.initials: CP
authors.lastname: Reynolds
authors.forename: Allen
authors.initials: A
authors.lastname: Buxton
authors.forename: Ralph A
authors.initials: RA
authors.lastname: Reisfeld
authors.forename: Steven D
authors.initials: SD
authors.lastname: Gillies
authors.forename: Susan L
authors.initials: SL
authors.lastname: Cohn
authors.forename: John M
authors.initials: JM
authors.lastname: Maris
authors.forename: Paul M
authors.initials: PM
authors.lastname: Sondel
mesh_terms: D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D004359:Drug Therapy, Combination; D005732:Gangliosides / Q000276:immunology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use; D006801:Humans; D007167:Immunotherapy / Q000009:adverse effects; D007223:Infant; D057194:Intention to Treat Analysis; D007376:Interleukin-2 / Q000627:therapeutic use; D015474:Isotretinoin / Q000627:therapeutic use; D009447:Neuroblastoma / Q000188:drug therapy / Q000401:mortality / Q000628:therapy*; D033581:Stem Cell Transplantation; D016019:Survival Analysis
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D005732:Gangliosides; D007376:Interleukin-2; C019403:ganglioside, GD2; C112746:dinutuximab; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D015474:Isotretinoin