Addition of rituximab to standard chemotherapy significantly prolonged event-free survival and overall survival in children and adolescents with high-grade, high-risk, mature B-cell non-Hodgkin lymphoma (NHL), according to findings published in The New England Journal of Medicine.
Investigators conducted an open-label, international, randomized, phase 3 trial (ClinicalTrials.gov Identifier: NCT01516580) to determine whether the addition of rituximab to standard lymphomes malins B (LMB) chemotherapy would improve outcomes in this pediatric and adolescent patient population. High-grade, high-risk, mature B-cell NHL was defined as stage III with an elevated lactate dehydrogenase level or stage IV, or acute leukemia.
A total of 328 eligible patients were randomly assigned (1:1) to receive 6 doses of rituximab with LMB chemotherapy (164 patients) or standard LMB chemotherapy alone (164 patients). The primary endpoint was event-free survival, and secondary endpoints included overall survival, toxicity, and immune reconstitution. The median follow-up was 39.9 months.
Of the entire cohort, 85.7% of patients had Burkitt lymphoma. Mean ages among patients in the rituximab-chemotherapy group and chemotherapy group were 8.6 years and 9.2 years, respectively. Patients were predominantly male (approximately 83% in both groups), and patient characteristics were well balanced between the 2 treatment groups.
A total of 38 events were observed: 10 in the rituximab–chemotherapy group and 28 in the chemotherapy group. At 3 years, the event-free survival was 93.9% in the rituximab–chemotherapy group and 82.3% in the chemotherapy group (hazard ratio [HR] for an event, 0.32; 95% CI, 0.15-0.66; one-sided P =.00096).
At 3 years, the overall survival was 95.1% in the rituximab–chemotherapy group and 87.3% in the chemotherapy group. Of the 28 total deaths, 8 occurred in the rituximab–chemotherapy group (4 disease related, 3 treatment related, and 1 second cancer) and 20 occurred in the chemotherapy group (17 disease related and 3 treatment related; HR for death, 0.36).
After prephase treatment, the incidence of grade 4 or higher acute adverse events (primarily febrile neutropenia and infection) was 33.3% in the rituximab–chemotherapy group and 24.2% in the chemotherapy group (P =.07). More patients in the rituximab–chemotherapy group had a low immunoglobulin G level compared to the chemotherapy group (at end of therapy, 70.3% vs 46.8%; P =.002; 1 year after the trial, 55.9% vs 25.4%; P <.001).
“This trial showed that the addition of rituximab to chemotherapy was effective therapy in children and adolescents with high-risk, high-grade, mature B-cell non-Hodgkin’s lymphoma and resulted in long-term complete remission in 95% of the patients,” wrote the authors. “In addition, we found an effective global framework for academic-based, collaborative pediatric groups that leveraged both public and private sector support to conduct clinical trials involving children with a rare cancer,” concluded the investigators.
Disclosures: Some authors have declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.
Minard-Colin V, Aupérin A, Pillon M, et al. Rituximab for high-risk, mature B-cell non-Hodgkin’s lymphoma in children. N Engl J Med. 2020;382(23):2207-2219.