Children and adolescents with mature B cell non-Hodgkin lymphomas (NHL) generally have good treatment outcomes. Nonetheless, those with high-risk disease continue to have worse outcomes, indicating a need for treatment intensification in this poor-prognosis subgroup. Now, data from a phase III trial demonstrate that adding the anti-CD20 antibody rituximab to the standard-of-care lymphomes malins B (LMB) regimen improves event-free survival (EFS) in this setting.

A total of 328 patients between 6 months and 18 years of age with newly diagnosed high-risk mature B cell neoplasms (of whom 85.7% had Burkitt lymphoma) were randomly assigned (1:1) to receive LMB chemotherapy either with or without rituximab. All patients received prephase chemotherapy, consisting of cyclophosphamide, vincristine and prednisone. The intensity of chemotherapy in both groups was then stratified based on the presence or absence of CNS-positive disease and/or extensive bone-marrow involvement (≥25%). EFS was the primary end point of this trial.

At a median follow-up duration of ~40 months in both arms, patients receiving rituximab plus chemotherapy had a significantly improved 3-year EFS rate (93.9% versus 82.3%, HR 0.32, 95% CI 0.15–0.66; P = 0.00096). Overall survival (OS) was also improved in patients receiving rituximab plus chemotherapy at this time point (HR for death 0.36, 95% CI 0.16–0.82).

Patients in the rituximab group had a significantly increased risk of adverse events, including acute rituximab-related infusion reactions in 33.3%, of which 4.3% were grade 3 in severity. Following completion of prephase chemotherapy, patients in the rituximab plus chemotherapy group had a higher, albeit statistically insignificant, risk of grade ≥4 adverse events (33.3% versus 24.2%; P = 0.07). Three patients in each group died of treatment-related adverse events.

These findings provide robust evidence that the addition of rituximab to chemotherapy improves EFS in children or adolescents with high-risk mature B cell neoplasms. Longer-term follow-up data are required to assess the extent to which this approach improves OS and the possibility of late-onset toxicities.