A Phase I/IIa Study of Antidisialoganglioside Antibody Dinutuximab in Japanese Patients With Neuroblastoma

J Pediatr Hematol Oncol. 2021 Apr 1;43(3):e358-e364. doi: 10.1097/MPH.0000000000001684.

Abstract

Japanese patients with neuroblastoma completing induction therapy and high-dose chemotherapy received antidisialoganglioside antibody dinutuximab 17.5 mg/m2 for 4 days during each of 5 consecutive 28-day cycles. Patients also received macrophage colony-stimulating factor (M-CSF) or granulocyte colony-stimulating factor (G-CSF) during cycles 1, 3, and 5 combined with interleukin-2 teceleukin during cycles 2 and 4. A total of 25 patients (11 in the M-CSF group and 14 in the G-CSF group) were enrolled, and dose-limiting toxicity was assessed in the first 12 patients (6 in each group). The recommended doses of dinutuximab, M-CSF, and G-CSF were determined to be 17.5 mg/m2, 6.0×106 U/m2, and 5 µg/kg/d, respectively, whereas that of teceleukin was 0.75×106 IU/m2 during week 1 and 1×106 IU/m2 during week 2. The most common grade 3 or 4 adverse events in both groups were neutrophil count decreased, platelet count decreased, pyrexia, and alanine aminotransferase increased. Four patients (2 in each group) discontinued the treatment because of adverse events. At the end of the study, survival was confirmed in 22 patients (9 in the M-CSF group and 13 in the G-CSF group). From these results, we concluded that this combination regimen is a feasible treatment for Japanese patients with neuroblastoma.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / therapeutic use*
  • Antineoplastic Agents, Immunological / adverse effects
  • Antineoplastic Agents, Immunological / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Child
  • Child, Preschool
  • Female
  • Granulocyte Colony-Stimulating Factor / adverse effects
  • Granulocyte Colony-Stimulating Factor / therapeutic use
  • Humans
  • Interleukin-2 / adverse effects
  • Interleukin-2 / therapeutic use
  • Japan / epidemiology
  • Macrophage Colony-Stimulating Factor / adverse effects
  • Macrophage Colony-Stimulating Factor / therapeutic use
  • Male
  • Neuroblastoma / drug therapy*
  • Neuroblastoma / epidemiology
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents, Immunological
  • Interleukin-2
  • Granulocyte Colony-Stimulating Factor
  • dinutuximab
  • Macrophage Colony-Stimulating Factor