On December 2, 2021, rituximab was approved for use in combination with chemotherapy for pediatric patients (≥ 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.1
Supporting Efficacy Data
Approval was based on interim analysis findings in the global open-label, phase III Inter-B-NHL Ritux 2010 trial (ClinicalTrials.gov identifier NCT01516580). Efficacy was assessed in 328 patients randomly assigned to Lymphome Malin B (LMB) chemotherapy (corticosteroids, vincristine, cyclophosphamide, high-dose methotrexate, cytarabine, doxorubicin, etoposide, and triple-drug [methotrexate/cytarabine/corticosteroid] intrathecal therapy) alone (n = 164) or in combination with rituximab or non-U.S. licensed rituximab (n = 164) given in six infusions of 375 mg/m2 (two doses during each of the two induction courses and one during each of the two consolidation courses).
The main efficacy outcome measure was event-free survival. With a median follow-up of 3.1 years, event-free survival events occurred in 10 patients in the rituximab/LMB group vs 28 in the LMB group (hazard ratio = 0.32, 90% confidence interval [CI] = 0.17–0.58, P = .0012). Death occurred in 8 vs 20 patients, with an estimated overall survival hazard ratio of 0.36 (95% CI = 0.16–0.81); no formal statistical test was conducted for overall survival, with the result considered descriptive.
How It Is Used
The recommended dose of rituximab is 375 mg/m2 via intravenous infusion given in combination with systemic LMB chemotherapy. A total of six infusions of rituximab are given: two during each of the two induction courses (COPDAM1 [cyclophosphamide, vincristine, prednisolone, doxorubicin, methotrexate] and COPDAM2) and one dose during each of the two consolidation courses of CYM (cytarabine, methotrexate) and CYVE (cytarabine, etoposide).
In the pivotal trial, the most common grade ≥ 3 adverse events in the rituximab/LMB group were febrile neutropenia (93% vs 91% in the LMB group), stomatitis (80% vs 75%), enteritis (24% vs 16%), sepsis (18% vs 13%), increased alanine aminotransferase (19% vs 14%), and hypokalemia (16% vs 13%). Serious adverse events occurred in 55% of the rituximab/LMB group, most commonly febrile neutropenia (15%), stomatitis (11%), and sepsis (8%). Adverse events led to discontinuation of rituximab in 2% of patients. Fatal adverse events occurred in 3% of patients, most commonly sepsis (2%).
Rituximab has boxed warnings for fatal infusion-related reactions, severe mucocutaneous reactions, hepatitis B virus reactivation, and progressive multifocal leukoencephalopathy. Rituximab also has warnings/precautions for tumor-lysis syndrome, infections, cardiac adverse reactions, renal toxicity, bowel obstruction and perforation, live virus vaccinations, and embryofetal toxicity. Patients should be advised not to breastfeed while receiving rituximab.
1. Rituxan (rituximab) injection, for intravenous use, prescribing information, Genentech. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/103705s5465lbl.pdf. Accessed December 10, 2021.