Rituximab Regimen Improves Survival in Children With Aggressive B-Cell Lymphoma

Adding rituximab (Rituxan, Truxima) to chemotherapy may be a new standard for treating children and young adults newly diagnosed with aggressive B-cell lymphoma, according to findings from a randomized, international, phase 3 trial.

Research published in New England Journal of Medicine found that the combination of rituximab with chemotherapy prolonged event-free survival (EFS) and overall survival (OS) among patients with high-grade, high-risk, mature B-cell non-Hodgkin lymphoma.

Rituximab is already considered the standard of care along with chemotherapy in most patients with high-grade B-cell non-Hodgkin lymphoma, the authors explained, with the therapy being effective in adults.

“The outcome in children and adolescents with B-cell non-Hodgkin’s lymphoma receiving chemotherapy alone is superior to that in adults; therefore, the potential benefits of rituximab must be balanced against potential unexpected and severe toxic effects,” the authors explained.

The researchers studied 328 patients who were randomized 1:1 to receive either rituximab in combination with chemotherapy or chemotherapy alone. The trial involved the European Intergroup for Childhood Non-Hodgkin Lymphoma and the Children’s Oncology Group and spanned 12 countries. EFS was the primary end point, and the 3-year EFS was expected to be 84% based on data from the FAB/LMB96 study, the authors noted.

The media follow up was 39.9 months (40.9 months in the rituximab—chemotherapy group and 39.1 months in the chemotherapy group). In total, there were 38 events: 10 in the rituximab–chemotherapy group and 28 in the chemotherapy group. Three patients in each group died from toxic events and 2 patients in each group had primary refractory disease.

EFS at 3 years was about what was expected in the chemotherapy group (82.3%; 95% CI, 75.7-87.5), but it was higher in the rituximab—chemotherapy group (93.9%; 95% CI, 89.1-96.7). OS was 95.1% (95% CI, 90,.5-97.5) in the rituximab–chemotherapy group compared with 87.3% (95% CI; 81.2-91.6) in the chemotherapy group.

Malcolm Smith, MD, PhD, of the National Cancer Institute (NCI)’s Cancer Therapy Evaluation Program, who was not involved in the study, said in an NCI blog post that the findings showed the treatment was “remarkably effective.”

“To achieve 95% survival for these patients is an outstanding result and a very important accomplishment,” he said.

During the first infusion of rituximab, the incidence of reactions related to the infusion was 33.3%; however, the incidence decreased significantly to 3.7% to 9.6% during subsequent infusions.

The most frequent adverse events (AEs) were febrile neutropenia (91.7% of all patients; 90.8% of chemotherapy group vs 92.6% of rituximab—chemotherapy group), stomatitis (77.5% overall; 75.2% of chemotherapy group vs 79.6% of rituximab–chemotherapy group), and infection (54.0% overall; 49.0% of chemotherapy group vs 58.6% of rituximab–chemotherapy group). In the rituximab–chemotherapy group, the incidence of AEs of grade 4 or higher was 37.7% compared with 32.7% in the chemotherapy group.

“This trial showed that the addition of rituximab to chemotherapy was effective therapy in children and adolescents with high-risk, high-grade, mature B-cell non-Hodgkin’s lymphoma and resulted in long-term complete remission in 95% of the patients,” the authors concluded. “In addition, we found an effective global framework for academic-based, collaborative pediatric groups that leveraged both public and private sector support to conduct clinical trials involving children with a rare cancer.”

Reference

Minard-Colin V, Aupérin A, Pullon M, et al, for the European Intergroup for Childhood Non-Hodgkin Lymphoma, and the Children’s Oncology Group. Rituximab for high-risk, mature B-cell non-Hodgkin’s lymphoma in children. N Engl J Med. 2020;382:2207-2219. doi:10.1056/NEJMoa1915315