Clinical Pearls & Morning Reports
Minard-Colin et al. conducted an international, randomized, phase 3 trial to establish whether the addition of rituximab to lymphomes malins B (LMB) chemotherapy could improve event-free survival among children and adolescents with high-grade, high-risk, mature B-cell non-Hodgkin’s lymphoma or leukemia. Read the NEJM Original Article here.
Q: How successful are current therapies for children and adolescents with high-grade, mature B-cell non-Hodgkin’s lymphoma?
A: Cure rates among children and adolescents with high-grade, mature B-cell non-Hodgkin’s lymphoma (mainly Burkitt’s lymphoma but also diffuse large B-cell lymphoma) have dramatically improved over the past 30 years, with trials showing survival of approximately 90%. However, well-known prognostic factors such as higher stage, elevated lactate dehydrogenase level, leukemic bone marrow, and central nervous system (CNS) involvement and treatment-related factors such as lack of early or complete response can identify patients at high risk for treatment failure.
Q: What considerations are relevant when one considers adding rituximab to chemotherapy for children and adolescents with B-cell non-Hodgkin’s lymphoma?
A: Rituximab has shown efficacy in adults with B-cell cancers, including diffuse large B-cell lymphoma and Burkitt’s lymphoma, and is considered to be the standard of care in addition to chemotherapy in most patients with high-grade B-cell non-Hodgkin’s lymphoma. 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. Furthermore, subtypes of mature B-cell non-Hodgkin’s lymphoma differ between adults and children in terms of molecular anomalies that may confer different prognoses and sensitivities to treatments.
A: In this randomized, international, phase 3 trial, the authors found that among children and adolescents with high-grade, high-risk mature B-cell lymphoma, the addition of six doses of rituximab to LMB therapy led to significantly better event-free survival outcomes (hazard ratio for an event, 0.32; 95% confidence interval (CI), 0.15 to 0.66; 3-year event survival, 93.9% in the rituximab–chemotherapy group vs. 82.3% in the chemotherapy group). The benefit was similar across the various therapeutic groups, including the group of patients with CNS disease. Higher 3-year overall survival was also observed (95.1% in the rituximab–chemotherapy group vs. 87.3% in the chemotherapy group; hazard ratio for death, 0.36; 95% CI, 0.16 to 0.82).
A: Overall, the acute toxic effects that were associated with the addition of rituximab mainly involved a higher incidence of myelotoxic effects, but further follow-up is needed to provide information on long-term safety because rituximab therapy induced more hypogammaglobulinemia than chemotherapy alone.