Rituximab for high-risk, mature B-cell non-Hodgkin’s lymphoma in children

Research output: Contribution to journalArticlepeer-review


  • V. Minard-Colin
  • A. Aupérin
  • M. Pillon
  • G. A.A. Burke
  • D. A. Barkauskas
  • R. F. Delgado
  • S. Alexander
  • A. Uyttebroeck
  • C. M. Bollard
  • J. Zsiros
  • M. Csoka
  • B. Kazanowska
  • A. K. Chiang
  • R. R. Miles
  • A. Wotherspoon
  • P. C. Adamson
  • G. Vassal
  • C. Patte
  • T. G. Gross

Colleges, School and Institutes

External organisations

  • Gustave Roussy
  • Université Paris-Saclay
  • University of Padova Dep. Pure and Applied Mathematics Via Trieste
  • University of Cambridge
  • University of Southern California Keck School of Medicine
  • Fundació General de la Universitat de Valencia (FGUV)
  • University of Toronto
  • Leuven Cancer Institute
  • George Washington University
  • Princess Máxima Center for Pediatric Oncology
  • Semmelweis University
  • Wroclaw Medical University
  • The University of Hong Kong
  • University of Utah
  • The Royal Marsden Hospital NHS Foundation Trust
  • Children’s Hospital of Philadelphia
  • National Cancer Institute


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.


Original languageEnglish
Pages (from-to)2207-2219
Number of pages13
JournalNew England Journal of Medicine
Issue number23
Publication statusPublished - 4 Jun 2020

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