Data from the first interim analysis of the randomized Intergroup trial addressing rituximab efficacy in addition to standard LMB chemotherapy in children with high-risk B-cell non-Hodgkin’s lymphoma (B-NHL) and mature acute leukemia (B-AL) has revealed beneficial effects.
The results were recently presented by Genentech at the American Society of Clinical Oncology (ASCO) 2016 Annual Meeting June 3-7 in Chicago in a presentation, “Results of the randomized Intergroup trial Inter-B-NHL Ritux 2010 for children and adolescents with high-risk B-cell non-Hodgkin lymphoma (B-NHL) and mature acute leukemia (B-AL): Evaluation of rituximab (R) efficacy in addition to standard LMB chemotherapy (CT) regimen.”
Rituximab is a monoclonal antibody that targets CD20, a molecule that is expressed at the surface of virtually all mature B-cells. Combination of rituximab with LMB chemotherapy regimen has been shown to improve survival in adult B-cell malignancies, but its efficacy and safety in children had not been assessed in a randomized trial.
The Intergroup Phase 3 randomized trial began in December 2011 to compare the effects of LMB chemotherapy regimen to LMB plus rituximab in patients under the age of 18 with high risk B-NHL and B-AL.
Patients received a total of four chemotherapy courses. Those who were randomized to the rituximab group received it two days before and one day after the first two chemotherapy courses and on day 1 of the two following courses.
The study had been designed to enroll 600 patients and required 72 events to detect the expected increase in event-free survival with the desired significance. The first interim analysis was performed in August 2015, when 310 patients randomized to LMB or LMB plus rituximab since the beginning of the study were analyzed. The analysis was based on 27 events, which accounted for 35.7 percent of the events required.
Among the examined patients, 85 percent had Burkitt lymphoma. Fifty-one percent were in stage 3 or 4, central nervous system (CNS) negative; 39 percent were stage 4/B-AL cerebrospinal fluid (CSF) negative; and 10 percent were CSF positive. The interim analysis showed that patients taking rituximab had a better one-year event-free survival than those on the control arm.
But the conditional power analysis of the study suggested a high likelihood of getting beneficial results in the final analysis, and as a result, the Independent Data Monitoring Committee recommended the study stop randomizing new patients in November 2015.