• European Intergroup for Childhood Non-Hodgkin Lymphoma the Children’s Oncology Group
  • Véronique Minard-Colin
  • Anne Aupérin
  • Marta Pillon
  • G A Amos Burke
  • Donald A Barkauskas
  • Keith Wheatley
  • Rafael F Delgado
  • Sarah Alexander
  • Anne Uyttebroeck
  • Catherine M Bollard
  • József Zsiros
  • Monika Csoka
  • Bernarda Kazanowska
  • Alan K Chiang
  • Rodney R Miles
  • Andrew Wotherspoon
  • Peter C Adamson
  • Gilles Vassal
  • Catherine Patte
  • Thomas G Gross

BACKGROUND: Rituximab added to chemotherapy prolongs survival among adults with B-cell cancer. Data on its efficacy and safety in children with high-grade, mature B-cell non-Hodgkin's lymphoma are limited.

METHODS: We conducted an open-label, international, randomized, phase 3 trial involving patients younger than 18 years of age with high-risk, mature B-cell non-Hodgkin's lymphoma (stage III with an elevated lactate dehydrogenase level or stage IV) or acute leukemia to compare the addition of six doses of rituximab to standard lymphomes malins B (LMB) chemotherapy with standard LMB chemotherapy alone. The primary end point was event-free survival. Overall survival and toxic effects were also assessed.

RESULTS: Analyses were based on 328 patients who underwent randomization (164 patients per group); 85.7% of the patients had Burkitt's lymphoma. The median follow-up was 39.9 months. Events were observed in 10 patients in the rituximab-chemotherapy group and in 28 in the chemotherapy group. Event-free survival at 3 years was 93.9% (95% confidence interval [CI], 89.1 to 96.7) in the rituximab-chemotherapy group and 82.3% (95% CI, 75.7 to 87.5) in the chemotherapy group (hazard ratio for primary refractory disease or first occurrence of progression, relapse after response, death from any cause, or second cancer, 0.32; 95% CI, 0.15 to 0.66; one-sided P = 0.00096, which reached the significance level required for this analysis). Eight patients in the rituximab-chemotherapy group died (4 deaths were disease-related, 3 were treatment-related, and 1 was from a second cancer), as did 20 in the chemotherapy group (17 deaths were disease-related, and 3 were treatment-related) (hazard ratio, 0.36; 95% CI, 0.16 to 0.82). The incidence of acute adverse events of grade 4 or higher after prephase treatment was 33.3% in the rituximab-chemotherapy group and 24.2% in the chemotherapy group (P = 0.07); events were related mainly to febrile neutropenia and infection. Approximately twice as many patients in the rituximab-chemotherapy group as in the chemotherapy group had a low IgG level 1 year after trial inclusion.

CONCLUSIONS: Rituximab added to standard LMB chemotherapy markedly prolonged event-free survival and overall survival among children and adolescents with high-grade, high-risk, mature B-cell non-Hodgkin's lymphoma and was associated with a higher incidence of hypogammaglobulinemia and, potentially, more episodes of infection. (Funded by the Clinical Research Hospital Program of the French Ministry of Health and others; number, NCT01516580.).

Original languageEnglish
Pages (from-to)2207-2219
Number of pages13
JournalN Engl J Med
Issue number23
Publication statusPublished - 4 Jun 2020

    Research areas

  • Adolescent, Antineoplastic Agents, Immunological/administration & dosage, Antineoplastic Combined Chemotherapy Protocols/adverse effects, Child, Child, Preschool, Female, Follow-Up Studies, Humans, Infections/etiology, Infusions, Intravenous, Kaplan-Meier Estimate, Lymphoma, B-Cell/drug therapy, Male, Neutropenia/chemically induced, Progression-Free Survival, Rituximab/administration & dosage

ID: 52277219