FDA Approves Rituximab Plus Chemotherapy for Pediatric B-NHL and B-AL

Rituximab in combination with chemotherapy is now FDA approved for the treatment of pediatric patients with 4 types of hematologic malignancies.

The FDA approved rituximab (Rituxan) in combination with chemotherapy for the treatment of pediatric patients aged 6 months to 18 years with previously untreated, advanced stage, CD20-positive diffuse large B-cell lymphoma, Burkitt lymphoma, Burkitt-like lymphoma, or mature B-cell acute leukemia (B-AL), according to an FDA press release.1

Approval of rituximab/chemotherapy for these multiple indications is supported by findings from the phase 3 Inter-B-NHL Ritux 2010 clinical trial (NCT01516580), which was an intergroup trial of children with the high-risk disease treated with rituximab plus chemotherapy or chemotherapy alone.

The goal of the study was to determine the efficacy and safety of the combination in B-cell non-Hodgkin lymphoma (B-NHL) and B-AL. The primary end point of the study was event-free survival (EFS), and the secondary end points were overall survival (OS), acute toxicity, and long-term toxicity.

Results published in 2016 from the Inter-B-NHL Ritux 2010 clinical trial showed that rituximab plus chemotherapy improved EFS in children and adolescents with high-risk B-NHL and B-AL. The findings were from 328 patients who received rituximab via intravenous infusion at a dose of 385 mb/m2 with chemotherapy or chemotherapy alone. At a median follow-up of 3.1 years, the rituximab arm had 28 EFS events compared with only 10 in the control arm (HR, 0.32; 90% CI, 0.17-0.58; P = .0012).2

In terms of the secondary end points, 20 patients in the experimental arm had died at the time of data cutoff compared with 8 patients in the control arm, showing an estimated HR for OS of 0.36 (95% CI, 0.16-0.81). The OS results were considered to be descriptive considering that no formal statistical test was performed during the study. After the interim analysis, randomization in the study was discontinued, but 122 patients were then evaluated for safety.

The adverse events (AEs) observed in the rituximab plus chemotherapy arm included febrile neutropenia, stomatitis, enteritis, sepsis, increased alanine aminotransferase, and hypokalemia. These AEs were grade 3 or higher in 15% of patients. Of the higher-grade AEs, sepsis, stomatitis, and enteritis occurred most frequently. Further, fatal AEs occurred in 2% of patients in both treatment arms.

Based on the study findings, the FDA has recommended a 375 mg/m2 dose of rituximab given via IV infusion with systemic Lymphome Malin B chemotherapy. Over the course of treatment, oncologists should administer 6 infusions of rituximab. Chemotherapy agents that should be used in combination with rituximab include cyclophosphamide, vincristine, doxorubicin, and cytarabine.


1. FDA approves rituximab plus chemotherapy for pediatric cancer indications. News release. FDA. December 3, 2021. Accessed December 3, 2021. https://bit.ly/3lv82kU

2. Minard-Colin V, Auperin A, Pillon M, et al. Results of the randomized Intergroup trial Inter-B-NHL Ritux 2010 for children and adolescents with high-risk B-cell non-Hodgkin lymphoma (B-NHL) and mature acute leukemia (B-AL): Evaluation of rituximab (R) efficacy in addition to standard LMB chemotherapy (CT) regimen. J Clin Oncol. 2016; 34(suppl 15): 10507-10507. doi: 10.1200/JCO.2016.34.15_suppl.10507