FDA Approves Rituximab Combination Across Multiple Pediatric Cancer Indications

FDA clears rituximab (Rituxan) plus chemotherapy for pediatric patients with treatment-naïve, advanced stage, CD20-positive diffuse large B-cell lymphoma, Burkitt’s lymphoma, Burkitt-like lymphoma, or adult B-cell acute leukemia.

FDA officials have approved rituximab (Rituxan) plus chemotherapy for pediatric patients with treatment-naïve, advanced stage, CD20-positive diffuse large B-cell lymphoma (DLBCL), Burkitt’s lymphoma (BL), Burkitt-like lymphoma (BLL) ) or adult B-cell acute leukemia (B-AL).

The approval was based on the global, multicenter, open-label Phase 3 Inter-B-NHL Ritux 2010 study (NCT01516580), which enrolled patients at least 6 months of age with treatment-naïve, advanced-stage, CD20-positive, DLBCL/BL /BLL/B-AL.

Patients were randomized 1:1 to receive Lymphoma Malin B (LMB) chemotherapy consisting of corticosteroids, vincristine, cyclophosphamide, high-dose methotrexate, cytarabine, doxorubicin, etoposide, and three-drug intrathecal therapy (methotrexate/cytarabine/corticosteroid), alone or in combination with rituximab or non-US-approved rituximab.

Patients in the study cohort received 6 infusions of intravenous rituximab at a dose of 375 mg/m2. 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 indicated by the detection of viable cells in residue after the second CYVE test. course of treatment (cytarabine/veposide), whichever came first.

In both cohorts, 83% of patients were male and 17.5% female with a median age of 7.5 years (range, 1-17). In the study arm, 0.6% of patients were 6 months to less than 3 years of age, 71.0% ranged from 3 years to less than 12 years of age, and 29% were 12 years to less than 18 years of age.

Forty-nine percent of patients in the rituximab arm had group B high-risk disease compared to 51.0% in the LMB chemotherapy arm; 40% of patients in both arms had group C1 disease and 11% vs. 10% of patients had group C3 disease. In both cohorts, most patients had BL or BLL, followed by B-AL and DLBCL. Furthermore, 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 receiving LMB chemotherapy alone compared to 10 events in patients receiving rituximab plus LMB chemotherapy (HR 0.32; 90% CI 0.17 -0.58;P=0.0012) .

At the time of the interim analysis, 20 deaths were reported in the LMB chemotherapy alone arm, compared to 8 deaths in the rituximab/LMB arm. Estimated overall survival HR was 0.36 (95% CI, 0.16-0.81).

An additional 122 patients received rituximab plus LMB and contributed to the safety analysis of the study. The most common adverse reactions in the rituximab combination cohort were febrile neutropenia, stomatitis, enteritis, sepsis, increased alanine aminotransferase and hypokalaemia.

Grade 3 or greater adverse reactions found to be more frequent in the rituximab-containing cohort than in the LMB cohort alone were sepsis, stomatitis, and enteritis. Lethal toxicities were experienced by less than 2% of those in both cohorts.

References

FDA clears rituximab plus chemotherapy for pediatric cancer indications. news item. FDA; December 2, 2021. Accessed December 2, 2021. https://bit.ly/3djDAGeRituxan. Prescribing information. Biogen and Genentech USA; 2021. Accessed December 2, 2021. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/103705s5465lbl.pdf

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