FDA Approves Rituximab/Chemo for Pediatric Cancer Indications

The FDA has approved rituximab 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.

The FDA has approved 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 efficacy of the combination was examined in the global, multicenter, open-label phase 3 Inter-B-NHL Ritux 2010 trial (NCT01516580). Study participants who were at least 6 months of age and had previously untreated, advanced stage, CD20-positive, DLBCL/BL/BLL/B-AL were randomized 1:1 to receive Lymphome Malin B (LMB) chemotherapy, which was comprised of corticosteroids, vincristine, cyclophosphamide, high-dose methotrexate, cytarabine, doxorubicin, etoposide, and triple-drug intrathecal therapy (methotrexate/cytarabine/corticosteroid), either alone or in combination with rituximab or non-US–licensed rituximab.

Those in the investigative arm received 6 infusions of intravenous rituximab at a dose of 375 mg/m2. Specifically, they were administered 2 doses during each of the 2 induction courses and 1 dose during each of the 2 consolidation courses, in accordance with the LMB scheme.2

The main efficacy outcome measure of the trial was event-free survival (EFS), which was 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. 

Investigators performed a prespecified interim efficacy analysis at 53% information fraction in 328 patients who had underwent randomization on the study (n = 164 in each arm). Across the treatment arms, 83% of patients were male and 17.5% were female. The median age was 7.5 years (range, 1-17). In the investigative arm, 0.6% of patients were aged 6 months to less than 3 years, 71.0% were aged 3 years to less than 12 years, and 29% were aged 12 years to less than 18 years.

Forty-nine percent of patients in the rituximab-containing arm had group B high-risk disease vs 51.0% of those on 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. The majority of patients, across the arms, had BL or BLL, followed by B-AL, and DLBCL. Across the arms, 45% of patients 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 vs 10 events in those who received 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 vs 8 deaths in the rituximab/LMB arm; the estimated overall survival (OS) HR was 0.36 (95% CI, 0.16-0.81). Notably, no formal statistical test was conducted for OS, and this result is considered to be descriptive. Randomization was discontinued after the interim analysis.

An additional 122 patients received rituximab plus LMB and contributed to the safety analysis of the trial. Results indicated that the most common adverse effects reported with the rituximab combination were febrile neutropenia, stomatitis, enteritis, sepsis, increased alanine aminotransferase, and hypokalemia.

Grade 3 or higher reactions noted to occur more frequently in the rituximab-containing arm vs the LMB-alone arm were sepsis, stomatitis, and enteritis. Fatal toxicities were experienced by less than 2% of those in both treatment arms.


  1. FDA approves rituximab plus chemotherapy for pediatric cancer indications. News release. FDA; December 2, 2021. Accessed December 2, 2021. https://bit.ly/3djDAGe
  2. Rituxan. Prescribing information. Biogen and Genentech USA; 2021. Accessed December 2, 2021. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/103705s5465lbl.pdf