Rituximab Boosts Chemotherapy Benefit in Patients with B-Cell Precursor ALL
In patients with B-cell precursor acute lymphoblastic leukemia (BCP-ALL), the addition of rituximab (Rituxan) to chemotherapy significantly improved event-free survival in a large European study.
“Adding rituximab to standard therapy should become a standard of care for these patients,” said Sébastien Maury, MD, Hôpital Henri Mondor, Créteil, France.
The study population included patients with Philadelphia chromosome–negative (Ph–), CD20-positive BCP-ALL. The GRAALL-R 2005 phase 3 clinical trial is the first randomized study to evaluate the role of rituximab in these patients.
“About one third of patients with BCP-ALL have CD20-positive ALL, and in these patients, the addition of rituximab is well-tolerated, significantly improves event-free survival, and also prolongs overall survival [OS] in patients not receiving allogeneic stem-cell transplant,” Dr Maury said.
Up to 40% of patients with BCP-ALL express CD20, which confers a worse prognosis and is targeted by rituximab.
The multicenter, randomized trial evaluated the potential benefit of adding rituximab to the pediatric-inspired GRAALL chemotherapy protocol in 220 patients with newly diagnosed CD20-positive, Ph– BCP-ALL.
After a median follow-up of 30 months, patients who received rituximab had a significantly lower cumulative incidence of relapse at 2 years (18%) versus patients in the control group (30.5%), who received only chemotherapy. No significant differences were observed in nonrelapse mortality.
The event-free survival rates at 2 years were 65% in the rituximab arm versus 52% in the control arm (P = .038). The OS rates, however, were not significantly different—71% with rituximab versus 64% without rituximab.
The exception was in the subset of patients who did not receive allogeneic stem-cell transplant in the first complete remission. In this group, the 2-year OS rate was 74% with rituximab versus 63% with chemotherapy alone (P = .018). In patients who were not going on to transplant, the infection-related serious adverse events were similar.
In discussing the presentation at the ASH plenary session, Adele K. Fielding, MBBS, PhD, Professor of Hematology, University College London, England, noted that no novel agents have been introduced for the routine upfront treatment of patients with Ph– ALL. Dr Fielding indicated that based on this study’s findings, rituximab could become this new drug.
She said that questions remain regarding the early and late toxicities for this combination, the types of patients most likely to benefit, the relationship between CD20 and response, and the correlation between minimal residual disease and response.
Press briefing moderator Robert A. Hromas, MD, MS, Chairman, Department of Medicine, University of Florida College of Medicine, Gainesville, commented that the benefit shown for rituximab “resolves a long-standing controversy” in this malignancy. “These results are exciting for those of us who treat leukemia,” Dr Hromas commented.