ORLANDO ­– Adding rituximab to the pediatric-inspired GRAALL protocol improved event-free survival in adults with CD20-positive, Philadelphia chromosome (Ph)-negative B-cell precursor acute lymphoblastic leukemia (BCP-ALL).1

The use of rituximab has significantly improved the treatment of patients with B-cell non-Hodgkin lymphoma and mature B-cell ALL who express CD20, which is also expressed in 30% to 50% of adult patients with BCP-ALL. Some single-arm studies have demonstrated that adding rituximab to chemotherapy may improve outcomes for these patients, but no randomized studies have evaluated this strategy.

“The GRAALL-R 2005 phase 3 study is the first randomized study evaluating the role of rituximab in these patients,” lead investigator Sébastien Maury, MD, PhD, of Hôpital Henri Mondor in France, said during the plenary session.

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For the multicenter trial, researchers enrolled 220 patients aged 18 to 59 years with newly diagnosed CD20-positive, Ph-negative BCP-ALL from 56 centers. Patients were randomly assigned to receive the pediatric-inspired GRAAL protocol with or without rituximab. Patients in the chemo-immunotherapy arm received rituximab 375 mg/m2 on days 1 and 7 of induction, on days 1 and 7 of salvage reinduction if needed, for 6 infusions during consolidation blocks, on days 1 and 7 of late intensification, and for 6 infusions during the first year of maintenance therapy for a total of 16 to 18 infusions. Patients were eligible to undergo allogeneic stem cell transplantation during first complete remission if patients had 1 or more conventional high-risk criteria and a donor.

“Eleven patients were excluded from the analysis because of non-eligibility criteria,” Dr Maury noted.

Results showed that 2-year event-free survival was 65% (95% CI, 56 – 75) in the rituximab arm compared with 52% (95% CI, 43 – 63) in the control arm (HR, 0.66; 95% CI, 0.45 – 0.98; P = .038) with a median follow-up of 30 months; however, there was no significant difference in 2-year overall survival or early response between the 2 treatment arms.

When adjusting for patients who received allogeneic stem cell transplantation during first complete remission, 2-year event-free survival and 2-year overall survival were significantly better in the rituximab arm (P = .021 and .018, respectively).

Subgroup analyses demonstrated no difference in event-free survival between the 2 arms among patients 40 years or older, patients with central nervous system involvement, patients with a white blood cell count 30 g/L or higher, or patients with CD20 expression 65% or higher.

In regard to safety, there was no significant difference in incidence of infection-related serious adverse events between non-transplanted patients in the rituximab arm and the control arm during any treatment phase. Of note, 11% of patients in the control arm experienced an allergic reaction vs 2% of those in the rituximab arm, suggesting that rituximab may provide protection against allergies, Dr Maury proposed.

“In these patients, the addition of rituximab to standard intensive chemotherapy is well-tolerated, significantly improves event-free survival, and prolongs overall survival of patients not receiving allogeneic stem cell transplantation in first complete remission. Adding rituximab to standard therapy should thus become a standard of care for these patients,” Dr Maury concluded. “The optimal dose schedule of rituximab administration remains to be determined.”


1. Maury S, Chevret S, Thomas X, et al. Addition of rituximab improves the outcome of adult patients with CD20-positive, Ph-negative, B-cell precursor acute lymphoblastic leukemia (BCP-ALL): results of the randomized GRAALL-R 2005 study. Oral presentation at: 57th American Society of Hematology (ASH) Annual Meeting & Exposition; December 5-8, 2015; Orlando, FL.