No Apparent Benefit of Rituximab After Lymphoma-Directed Conditioning and Allogeneic Stem Cell Transplantation for Relapsed/Refractory Aggressive NHL
In an open-label phase II trial reported in The Lancet Oncology, Glass et al examined the strategy of adding rituximab (Rituxan) to standard prophylaxis for graft-vs-host disease after allogeneic stem cell transplantation in relapsed or refractory aggressive non-Hodgkin lymphoma. Rituximab did not appear to reduce graft-vs-host disease or improve survival.
Study Details
The study included 84 patients with aggressive B-cell or T-cell lymphoma and primary refractory disease, early relapse (< 12 months after first-line treatment), or relapse after autologous transplantation at seven German centers. Patients were randomly assigned between June 2004 and March 2009 to rituximab at 375 mg/m² on days 21, 28, 35, 42, 175, 182, 189, and 196 (n = 42) or no rituximab (n = 42) after a lymphoma-directed myeloablative conditioning regimen and autologous transplantation. The conditioning regimen consisted of fludarabine (125 mg/m²), busulfan (12 mg/kg oral or 9.6 mg/kg IV), and cyclophosphamide (120 mg/kg). The primary endpoints were the incidence of acute graft-vs-host disease of grade 2 to 4 in each treatment group and overall survival at 1 year in both groups combined.
No Improvement in Graft-vs-Host Disease
The cumulative incidence of grade 2 to 4 acute graft-vs-host disease was 46% (95% confidence interval [CI] = 32%–62%) in the rituximab group and 42% (95% CI = 29%–59%) in the no rituximab group (hazard ratio [HR] = 0.91, P = .74). The cumulative incidence of extensive chronic graft-vs-host disease at 3 years was 33% and 41% (HR = 0.91, P = .28). Overall survival at 1 year for the whole study population was 52% (95% CI = 41%-62%). After median follow-up of 4.0 years, 40% of patients were alive (16 in the rituximab group and 18 in the control group).
Grade 4 hematologic adverse events and grade 3 alopecia occurred in all patients. Grade 3 or 4 infection occurred in 60% of the rituximab group and 76% of the control group. The most common nonhematologic grade 5 adverse events were pneumonia (10 vs 9 patients) and other infections (4 vs 7 patients).
The investigators concluded, “The lymphoma-directed myeloablative conditioning regimen developed here is promising for patients with refractory and relapsed aggressive B-cell and T-cell lymphomas. However, the addition of rituximab did not affect the incidence of [graft-vs-host disease] or overall survival.”
Norbert Schmitz, MD, of Asklepios Hospital St Georg, Hamburg, is the corresponding author for The Lancet Oncology article.
The study was funded by Hoffmann-La Roche, Amgen, and Astellas Pharma. Bertram Glass, MD, Michael Pfreundschuh, MD, Lorenz Truemper, MD, PhD, and Norbert Schmitz, MD, have served as consultants and received honoraria from Roche.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
