FDA Approves Rituximab Plus Chemo for Certain Pediatric Cancers

On December 2, 2021, the FDA approved the combination of rituximab (Rituxan, Genentech Inc.) plus chemotherapy for previously untreated pediatric patients (≥6 months to <18 years) with advanced stage CD20-positive diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma (BK), Burkitt-like lymphoma (BLL), or mature B-cell acute leukemia (B-AL).

This approval was based on efficacy outcomes from the phase 3 Inter-B-NHL Ritux 2010 trial of patients 6 months or older with previously untreated, advanced stage CD20-positive DLBCL, BL, BLL, and B-AL. A prespecified interim efficacy analysis found that at a median follow-up of 3.1 years, there were 28 event-free survival (EFS) events in the Lymphome Malin B (LMB) cohort, compared with 10 in the rituximab-LMB group (HR 0.32; 90% CI, 0.17-0.58; P=0.0012).

A total of 20 deaths occurred in the LMB chemotherapy arm compared with 8 deaths in the rituximab plus LMB chemotherapy arm, with an estimated overall survival (OR) HR of 0.36 (95% CI, 0.16-0.81). There was no formal statistical test conducted for OS, and the result is meant to be descriptive.

The most common (grade ≥3, >15%) adverse reactions for pediatric patients treated with rituximab and chemotherapy include febrile neutropenia, stomatitis, enteritis, sepsis, increased alanine aminotransferase, and hypokalemia. Additionally, grade ≥3 adverse reactions that occurred more in the rituximab plus LMB chemotherapy arm compared with the LMB chemotherapy arm included sepsis, stomatitis, and enteritis. Fatal adverse reactions happened in <2 percent of patients in both arms.

The FDA said the recommended rituximab dose is 375 mg/m2 intravenously in combination with systemic LMB chemotherapy. In total, 6 infusions of rituximab are administered, 2 doses during each of the induction courses, COPDAM1 (cyclophosphamide, vincristine, prednisone, doxorubicin, methotrexate) and COPDAM2, and 1 dose during each of the 2 consolidation courses of CYM (cytarabine, methotrexate) and CYVE.—Emily Bader

Source: US Food and Drug Administration. FDA approves rituximab plus chemotherapy for pediatric cancer indications. December 2, 2021. www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-rituximab-plus-chemotherapy-pediatric-cancer-indications. Accessed December 3, 2021.