The anti-CD20 monoclonal antibody rituximab is an integral component of chemoimmunotherapy regimens in B-cell non-Hodgkin lymphoma and mature B-cell acute lymphoblastic leukemia (ALL). However, its role in B-cell precursor (BCP)-ALL has not been established in randomized studies. Maury and colleagues reported the results of the multicenter randomized Graall-R 2005 trial that evaluated the efficacy and safety benefit of adding rituximab to the GRAALL protocol versus chemotherapy alone in patients with newly diagnosed CD20-positive (>20% leukemia blasts) Philadelphia chromosome (Ph)-negative BCP-ALL.1 In this trial, rituximab (375 mg/m2) was administered during induction (days 1 and 7), salvage reinduction when needed (days 1 and 7), consolidation (6 infusions), late intensification (days 1 and 7), and first year of maintenance (6 infusions); the primary end point was event-free survival (EFS). A total of 209 patients were analyzed in the modified intent-to-treat (ITT) data set (rituximab, n = 105; chemotherapy, n = 104). The median age of the study population was 40.2 years; the 2 treatment arms were well-balanced. Overall, complete response (CR) rates were similar between the 2 arms (92% vs 90%) following induction ± salvage reinduction; however, a significantly higher proportion of patients underwent allogeneic stem-cell transplantation (SCT) in first CR in the rituximab arm (34% vs 20%; P = .029). In patients who achieved CR after the first induction and were evaluated for minimal residual disease (MRD) level, the rates of MRD (<10-4) were similar between the 2 arms after induction and consolidation. At a median follow-up of 30 months, the rituximab-treated cohort had a significantly lower 2-year cumulative incidence of relapse (18% vs 32%; P = .018); however, rates of nonrelapse mortality were similar between the 2 treatment arms. The rituximab-treated group had a significantly longer 2-year EFS (65% vs 52%; hazard ratio [HR], 0.66; P = .038) compared with the control, which did not translate into a significant improvement in 2-year overall survival (OS), although it was numerically higher (71% vs 64%; HR, 0.70; P = .095). After patients who underwent allogeneic SCT in first CR were censored, rituximab-based therapy was found to be associated with a significantly longer 2-year EFS (66% vs 53%; HR, 0.59; P = .021) and 2-year OS (74% vs 63%; HR, 0.55; P = .018). Overall, 246 serious adverse events (SAEs) were reported in 124 patients, which were similar in both treatment arms except for a significantly lower incidence of allergic reactions in the rituximab arm. Based on these results, it was concluded that the addition of rituximab to the modified GRAALL protocol improved survival outcomes in adults with CD20-positive, Ph-negative, BCP-ALL, and that it should be considered as the standard of care in this setting.
