Rituximab Plus Chemotherapy Approved for Pediatric Blood Cancers

The U.S. Food and Drug Administration (FDA) has approved rituximab, in combination with chemotherapy, for the treatment of pediatric patients with the following previously untreated, advanced-stage cancer indications:

• CD20-positive diffuse large B-cell lymphoma (DLBCL)
• Burkitt lymphoma (BL)
• Burkitt-like lymphoma (BLL)
• mature B-cell acute leukemia (B-AL)

Approval is based on efficacy data from the Inter-B-NHL Ritux 2010 study of patients 6 months of age and older with previously untreated, advanced-stage, CD20-positive DLBCL, BL, BLL, or B-AL. Patients were randomized to receive either:

• Lymphome Malin B (LMB) chemotherapy alone (corticosteroids, vincristine, cyclophosphamide, high-dose methotrexate, cytarabine, doxorubicine, etoposide, and triple-drug [methotrexate/cytarabine/corticosteroid] intrathecal therapy])
• LMB in combination with 6 infusions of IV rituximab 375 mg/m²

The primary endpoint of the study was event-free survival (EFS). Events were defined as progressive disease, relapse, second malignancy, death, or nonresponse as evidenced by the detection of viable cells in residue after the second course of cytarabine. An interim efficacy analysis of 328 randomized patients with a median follow-up of 3.1 years found that among patients in the LMB only group, there were 28 events, compared with 10 events in the rituximab-LMB group.

At the time of the interim analysis, 20 patients died in the LMB-only arm, compared with 8 patients in the rituximab-LMB arm. After the interim analysis, randomization was discontinued. An additional 122 patients were then treated with rituximab-LMB and included in the safety analysis.

The most common adverse events (AEs), occurring in >15% of patients treated with rituximab plus chemotherapy, were febrile neutropenia, stomatitis, enteritis, sepsis, increased alanine aminotransferase, and hypokalemia. More patients in the rituximab-LMB arm experienced grade 3 or higher sepsis, stomatitis, and enteritis than in the LMB-only arm. In both the rituximab-LMB and LMB-only arms, fatal AEs occurred in <2% of patients.

Source: FDA.gov, December 2, 2021.