The Food and Drug Administration (FDA) has approved Rituxan (rituximab) in combination with chemotherapy for the treatment of patients 6 months of age and older with previously untreated, advanced stage, CD20-positive, diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma (BL), Burkitt-like lymphoma (BLL), or mature B-cell acute leukemia (B-AL).
The approval was based on data from the open-label, randomized phase 3 Inter-B-NHL Ritux 2010 trial (ClinicalTrials.gov Identifier: NCT01516580), which evaluated the efficacy and safety of rituximab in combination with chemotherapy in 362 patients 6 months of age and older with previously untreated, advanced stage, CD20-positive, DLBCL, BL, BLL, and B-AL.
Patients were randomly assigned to receive 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 (n=164).
The primary endpoint was event-free survival (EFS); an event was defined as occurrence of progressive disease, relapse, second malignancy, death from any cause, or nonresponse as evidenced by detection of viable cells in residue after the second cytarabine/etoposide course.
Interim analysis showed that after a median follow-up of 3.1 years, there were 28 events in the LMB chemotherapy arm and 10 events in the rituximab plus LMB arm (hazard ratio 0.32; 90% CI, 0.17-0.58; P =.0012). As of data cutoff date on December 31, 2017, there were 20 deaths reported in the LMB arm and 8 deaths in the rituximab plus LMB arm, with an estimated overall survival (OS) hazard ratio of 0.36 (95% CI, 0.16-0.81). The OS result is considered descriptive because a formal statistical test was not conducted for OS.
The most common adverse reactions of grade 3 or higher for rituximab plus LMB chemotherapy were febrile neutropenia, stomatitis, enteritis, sepsis, increased alanine aminotransferase, and hypokalemia.
- FDA approves rituximab plus chemotherapy for pediatric cancer indications. News release. December 3, 2021. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-rituximab-plus-chemotherapy-pediatric-cancer-indications.
- Rituxan. Package insert. Genentech; 2021. December 3, 2021. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/103705s5465lbl.pdf.