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Consolidation Treatment With Chimeric Anti-GD2-Antibody ch14.18 in Children Older Than 1 Year With Metastatic Neuroblastoma

From the Children's Hospital, University of Cologne, Cologne; Institute for Medical Biostatistics, Epidemiology, and Informatics, University of Mainz, Mainz; Children's Hospital, Medical School of Hanover, Hanover; Children's Hospital, University of Tübingen, Tübingen, Germany; St Jude Children's Research Hospital, Memphis, TN

Address reprint requests to Thorsten Simon, MD, Children's Hospital, Department of Pediatric Oncology and Hematology, University of Cologne, Joseph-Stelzmann-Straße 9, 50924 Köln, Germany; e-mail: thorsten.simon{at}uk-koeln.de

PURPOSE: Antibody treatment is considered tolerable and potentially effective in the therapy of neuroblastoma. We have analyzed stage 4 neuroblastoma patients older than 1 year who underwent consolidation treatment with the chimeric monoclonal anti-GD2-antibody ch14.18.

PATIENTS AND METHODS: Stage 4 patients older than 1 year who completed initial treatment without event were eligible. ch14.18 was scheduled in a dose of 20 mg/m²/d during 5 days in six cycles every 2 months. Patients who did not receive ch14.18 served as controls.

RESULTS: Of 334 assessable patients, 166 received ch14.18, 99 received a 12-month low-dose maintenance chemotherapy (MT) instead, and 69 had no additional treatment. During 695 ch14.18 cycles, fever (55% of cycles), abnormal C-reactive protein without infection (35%), cough (24%), rash (22%), and pain (16%) were the main side effects. Univariate analysis found similar event-free survival (EFS) for the three groups (3-year EFS, 46.5% ± 4.1%, 44.4% ± 4.9%, 37.1% ± 5.9% for patients treated with antibody ch14.18, MT, and no additional therapy, respectively; log-rank test, P = .314). For overall survival (OS), ch14.18 treatment (3-year OS, 68.5% ± 3.9%) was superior to MT (3-year OS, 56.6% ± 5.0%) or no additional therapy (3-year OS, 46.8% ± 6.2%; log-rank test, P = .018). Separate univariate analysis of patients with autologous stem-cell transplantation revealed no difference between patients with ch14.18 treatment and no additional consolidation. Multivariate analysis failed to demonstrate an advantage of antibody treatment for EFS and OS.

CONCLUSION: Consolidation treatment of stage 4 neuroblastoma with ch14.18 was associated with considerable but manageable side effects. Compared with oral maintenance chemotherapy and no consolidation treatment, ch14.18 had no clear impact on the outcome of patients.

The neuroblastoma trials were supported by Deutsche Krebshilfe. The antibody production was sponsored by Deutsche Leukämieforschungshilfe and Merck.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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