The addition of rituximab to standard lymphoma malins B (LMB) chemotherapy markedly prolonged event-free and overall survival (OS) in pediatric patients with high-grade, high-risk, mature B-cell non-Hodgkin’s lymphoma (NHL), an international phase III trial showed.
“Rituximab… is considered to be the standard of care in addition to chemotherapy in most [adult] patients with high-grade B-cell non-Hodgkin’s lymphoma,” Veronique Minard-Colin, MD, PhD, Gustave Roussy, Villejuif, France, and colleagues reported in The New England Journal of Medicine. “The benefit of rituximab therapy in this trial appeared to be similar to that observed in trials involving adult patients.”
In a cohort of 328 patients, event-free survival at three years was 68% longer at 93.9% (95% CI, 89.1-96.7%) in the rituximab-chemotherapy arm compared with 82.3% (95% CI, 75.7-87.5) in the chemotherapy alone group with a Hazard Ratio (HR) of 0.32 (95% CI, 0.15-0.66; P=0.00096), Minard-Colin and colleagues reported.
Again at three years, OS was 64% longer at 95.1% (95% CI, 90.5-97.5%) in the rituximab-chemotherapy group versus 87.3% (95% CI, 81.2-91.6%) in the chemotherapy group with an HR of 0.36 (95% CI, 0.16-0.82), investigators added.
However, despite these results, the study authors explained that the treatment comes with severe adverse side effects, noting “that while the trial showed a benefit with the addition of rituximab in the treatment of children with high-grade, high-risk, mature B-cell non-Hodgkin’s lymphoma, the use of rituximab in children with standard-risk B-cell non-Hodgkin’s lymphoma (approximately 40% of patients) is still questionable because their survival after treatment with chemotherapy alone is very high (97 to 98%).”
Inter-B-NHL Ritux 2010
The Inter-B-NHL Ritux 2010 trial involved children from 6 months to 18 years of age with newly diagnosed, high-grade, mature B-cell neoplasms including Burkitt’s lymphoma, diffuse large B-cell lymphoma, or high-grade, mature B-cell non-Hodgkin’s lymphoma not otherwise specified. Over 85% of the study group had Burkitt’s lymphoma.
The mean age of patients in the rituximab-chemotherapy group was 9.2 years versus 8.6 years for those in the chemotherapy alone group. All patients had advanced stage III disease with a lactate dehydrogenase (LDH) level more than twice the upper limit of normal or any stage IV disease or leukemia presentation.
Chemotherapy was administered according to the French-American-British (FAB)/LMB96-based protocol, with some minor modifications.
“All the patients received prephase treatment with low-dose cyclophosphamide, vincristine and prednisone (COP) regimen,” investigators noted, although there were a number of different groups in the study and subsequent treatments did vary between the groups.
Rituximab was given intravenously at a dose of 375 mg/m2 on day two before (i.e., day −2) and day one of each of the two induction chemotherapy courses and again on day one of each of the two consolidation courses, for a total of six doses, researchers explained.
Event-free survival, the primary end point of the study, was defined as the time between randomization and the detection of residual viable tumor cells after patients had received the second course of consolidation therapy.
At a median follow-up of 39.9 months, “there were 38 events: 10 in the rituximab-chemotherapy group and 28 in the chemotherapy group,” investigators noted.
The major difference between the two groups were in the rates of relapse or progression, which occurred in only three patients on the rituximab-chemotherapy arm and in 23 patients on the chemotherapy arm.
Moreover, all patients who relapsed or progressed did so within nine months of randomization.
Serious Adverse Events
The incidence of grade 4 or higher adverse events (AEs) overall was similar between the two groups at 37.7% in the rituximab-chemotherapy group and 32.7% in the chemotherapy alone group.
However, after patients received COP during the prephase treatment interval, the incidence of grade 4 or higher AEs was significantly higher in the dual agent arm at 33.3% compared with 24.2% for the single agent arm (P=0.07).
The incidence of grade 4 febrile neutropenia was also higher at 11.7% in the rituximab-chemotherapy group versus 6.5% in the chemotherapy group (P=0.11).
Overall, 1.8% of patients died from toxic events—three patients in each group, investigators noted.
Furthermore, at the end of treatment, more patients who received additional rituximab had a low IgG level than those who received chemotherapy alone at 70.3% versus 46.8%, respectively (P=0.002), as well as at 1 year at 55.9% versus 25.4%, respectively (P<0.0001).
Roughly twice as many patients in the dual agent arm also received intravenous immune globulin at 15.8% compared to 7% of those in the chemotherapy arm.
“The data from this trial suggest that the addition of rituximab may result in a higher incidence of severe (grade ≥4) acute adverse events (primarily febrile neutropenia and infection) after prephase treatment,” investigators cautioned.
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The addition of rituximab to standard chemotherapy markedly prolonged event-free and overall survival in pediatric patients with high-risk NHL.
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Survival gains with additional rituximab came at a cost of higher severe adverse event rates compared with chemotherapy alone.
Pam Harrison, Contributing Writer, BreakingMED™
Supported by a grant from the Clinical Research Hospital Program of the French Ministry of Health, by Cancer Research UK, the National Institute for Health Research Clinical Research Network, and Children’s Cancer Foundation Hong Kong, by grants from the U.S. National Cancer Institute, and by F. Hoffmann–La Roche–Genentech.
Minard-Colin reported receiving grant support, paid to her institution, from F. Hoffmann–La Roche; Dr. Aupérin, receiving grant support, paid to her institution, from F. Hoffmann-La Roche.
Cat ID: 467
Topic ID: 78,467,730,467,138,192,925
