Rituximab regimen extends EFS, OS in pediatric non-Hodgkin lymphoma subset
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The addition of rituximab to standard lymphomes malins B chemotherapy improved EFS and OS among a subset of pediatric patients with non-Hodgkin lymphoma, according to study results published in The New England Journal of Medicine.
The regimen — evaluated among children and adolescents with high-grade, high-risk mature B-cell non-Hodgkin lymphoma — also appeared associated with higher incidence of hypogammaglobulinemia and potentially more episodes of infection, results of the randomized phase 3 trial showed.
“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,” Véronique Minard-Colin, MD, PhD, clinical researcher at Institut Gustave Roussy in France, and colleagues wrote. “A phase 2 trial involving children showed that rituximab was active as a single-agent therapy for high-grade, high-risk, mature B-cell non-Hodgkin lymphoma and could be safely added to the lymphomes malins B (LMB) chemotherapy regimen.”
The study included 328 patients aged younger than 18 years with stage III or stage IV high-risk, mature B-cell non-Hodgkin lymphoma or acute leukemia.
Researchers assigned 164 patients to six doses of rituximab (Rituxan; Genentech, Biogen) in combination with standard LMB chemotherapy. The other 164 patients received standard LMB chemotherapy alone.
Most patients (85.7%) had Burkitt’s lymphoma. Patients with stage III disease also had elevated lactate dehydrogenase levels.
EFS served as the primary endpoint. Researchers also assessed OS and toxicity.
Median follow-up was 39.9 months.
Results showed 10 events among patients assigned the combination and 28 events among patients assigned chemotherapy alone.
Researchers reported 3-year EFS rates of 93.9% (95% CI, 89.1-96.7) in the combination group and 82.3% (95% CI, 75.7-87.5) in the chemotherapy-alone group. HR for primary refractory disease or first occurrence of progression, relapse after response, death of any cause or second cancer was 0.32 (95% CI, 0.15-0.66).
Eight patients in the combination group died. These included four deaths related to disease, three related to treatment and one due to a second cancer. In contrast, 20 patients in the chemotherapy group died; these included 17 deaths related to disease and three related to treatment.
Three-year OS rates were 95.1% (95% CI, 90.5-97.5) in the combination group and 87.3% (95% CI, 81.2-91.6) in the chemotherapy group (HR for death = 0.36; 95% CI, 0.16-0.82).
Incidence of grade 4 or higher acute adverse events after pre-phase treatment was 33.3% in the combination group and 24.2% in the chemotherapy-alone group. These mainly consisted of febrile neutropenia (11.7% vs. 6.5%) and infection (18.5% vs. 11.1%).
More than twice as many patients in the combination group than chemotherapy-alone group had a low immunoglobulin G level 1 year after trial inclusion (55.9% vs. 25.4%; P < .001).
“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 lymphoma and resulted in long-term complete remission in 95% of the patients,” Minard-Colin and colleagues wrote. “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.”
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Minard-Colin V, et al. N Engl J Med. 2020;doi:10.1056/NEJMoa1915315.
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