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Adding rituximab to a chemotherapy regimen can improve event-free survival (EFS) in adults with newly diagnosed, CD20-positive acute lymphoblastic leukemia (ALL), according to the GRAALL-2005/R study.
The 2-year EFS was significantly higher for patients who received rituximab than for those who received chemotherapy alone.
However, there was no significant difference between the groups in 2-year overall survival.
Sébastien Maury, MD, PhD, of Hȏpital Hénri Mondor in Creteil, France, and his colleagues reported these results in NEJM. Results from this study were previously presented at the 2015 ASH Annual Meeting.
The study included 209 patients with newly diagnosed, Ph-negative, B-cell precursor ALL with 20% or more CD20-positive leukemic blasts.
The patients’ median age was 40.2 (range, 24.5–52.6), 13% had an ECOG performance status greater than 1, 6% had CNS involvement, and 21% had a white blood cell count of 30 x 109/L or higher.
Half of the patients (n=104) were randomized to receive the GRAALL-2005 regimen, and the other half (n=105) were randomized to receive the same regimen plus rituximab. Details on the regimens are available in the supplementary material published with the NEJM paper.
Baseline patient characteristics were well-balanced between the treatment groups.
Results
At a median follow-up of 30 months, 101 patients (48%) had at least 1 event, including 44 (42%) in the rituximab group and 57 (55%) in the control group.
There were 17 induction failures (8 in the rituximab group and 9 in the control group), 57 relapses (22 and 35, respectively), and 27 deaths during remission (14 and 13, respectively). Two patients in the rituximab group were lost to follow-up during the first 12 months.
The 2-year EFS was significantly higher in the rituximab group than the control group—65% and 52%, respectively (hazard ratio [HR]=0.66, P=0.04).
However, the EFS benefit did not translate into a significant improvement in overall survival. The 2-year overall survival was 71% in the rituximab group and 64% in the control group (HR=0.70, P=0.10).
Similarly, the cumulative incidence of death during first remission was not significantly different between the treatment groups—12% for both (HR=0.98, P=0.96).
The researchers said the difference in EFS was mostly due to a lower incidence of relapse in the rituximab group. The 2-year incidence of relapse was 18% in the rituximab group and 32% in the control group (HR=0.52, P=0.02).
In a multivariate analysis, receiving the control treatment, older age, higher white blood cell count at baseline, and CNS involvement were all significantly associated with poor EFS.
There were 245 severe adverse events (AEs) reported in 124 patients—67 patients with 1 event, 26 with 2 events, 13 with 3 events, and 18 with 4 or more events.
The overall incidence of severe AEs did not differ significantly between the treatment groups—96% in the rituximab group and 92% in the control group.
Severe AEs included infection, laboratory abnormalities, allergic reactions, neurologic events, pulmonary events, coagulopathy, cardiac events, gastrointestinal events, and “other” events.
The only severe AE for which there was a significant difference between the treatment groups was allergic reactions. There were 2 severe allergic events in the rituximab group and 14 in the control group (P=0.002). Of these 16 events, all but 1 were due to asparaginase.
The researchers therefore theorized that rituximab might inhibit B-cell protection of antibodies against asparaginase, although they could not confirm this hypothesis.
