FDA approves rituximab (Rituxan) plus chemotherapy for pediatric patients with previously untreated, advanced stage, CD20-positive diffuse large B-cell lymphoma, Burkitt lymphoma, Burkitt-like lymphoma, or mature B-cell acute leukemia.
Officials with the FDA have granted approval to rituximab (Rituxan) plus chemotherapy for pediatric patients 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).1
The approval was based on the global, multicenter, open-label phase 3 Inter-B-NHL Ritux 2010 trial (NCT01516580), which enrolled patients at least 6 months of age with previously untreated, advanced stage, CD20-positive, DLBCL/BL/BLL/B-AL.
Patients were randomized 1:1 to receive Lymphome Malin B (LMB) chemotherapy consisting of corticosteroids, vincristine, cyclophosphamide, high-dose methotrexate, cytarabine, doxorubicin, etoposide, and triple-drug intrathecal therapy (methotrexate/cytarabine/corticosteroid), alone or in combination with rituximab or non-US–licensed rituximab.
Patients in the investigative cohort were administered 6 infusions of intravenous rituximab at a dose of 375 mg/m.2 The main efficacy outcome measure was event-free survival (EFS) defined as progressive disease, relapse, second malignancy, death from any cause, or non-response as evidenced by the detection of viable cells in residue after the second CYVE (cytarabine/veposide) course, whichever occurred first.
Across both cohorts, 83% of patients were male and 17.5% were female with a median age of 7.5 years (range, 1-17). In the investigative arm, 0.6% of patients were 6 months to less than 3 years of age, 71.0% ranged from 3 years of age to less than 12 years of age, and 29% were aged 12 years to less than 18 years.
Forty-nine percent of patients in the rituximab arm had group B high-risk disease compared with 51.0% in the LMB chemotherapy–alone arm; 40% of patients in both arms had group C1 disease and 11% vs 10% of patients, respectively, had group C3 disease. Across both cohorts, most patients had BL or BLL, followed by B-AL, and DLBCL. Further, 45% of patients in both cohorts had bone marrow involvement and 27% had central nervous system involvement.
At a median follow-up of 3.1 years, 28 EFS events were reported in those who received LMB chemotherapy alone compared with 10 events in patients administered rituximab plus LMB chemotherapy (HR 0.32; 90% CI, 0.17-0.58; P = .0012).
At the time of the interim analysis, 20 deaths were reported in the LMB chemotherapy–alone arm compared with 8 deaths in the rituximab/LMB arm. Estimated overall survival HR was 0.36 (95% CI, 0.16-0.81).
An additional 122 patients were administered rituximab plus LMB and contributed to the safety analysis of the trial. The most common adverse effects (AEs) in the rituximab combination cohort were febrile neutropenia, stomatitis, enteritis, sepsis, increased alanine aminotransferase, and hypokalemia.
Grade 3 or higher AEs noted to occur more frequently in the rituximab-containing cohort compared with the LMB-alone cohort were sepsis, stomatitis, and enteritis. Fatal toxicities were experienced by less than 2% of those in both cohorts.