Rituximab prophylaxis prevents corticosteroid-requiring chronic GVHD after allogeneic peripheral blood stem cell transplantation: results of a phase 2 trial

Abstract

B cells are implicated in the pathophysiology of chronic graft-vs-host disease (GVHD), and phase 2 trials suggest that B cell depletion can treat established chronic GVHD. We hypothesized that posttransplantation B cell depletion could prevent the occurrence of chronic GVHD. We performed a 65-patient phase 2 trial of rituximab (375 mg/m(2) IV), administered at 3, 6, 9, and 12 months after transplantation. Rituximab administration was safe without severe infusional adverse events. The cumulative incidences of chronic GVHD and systemic corticosteroid-requiring chronic GVHD at 2 years from transplantation were 48% and 31%, respectively, both lower than the corresponding rates in a concurrent control cohort (60%, P = .1, and 48.5%, P = .015). There was no difference in relapse incidence, but treatment-related mortality at 4 years from transplantation was significantly lower in treated subjects when compared with controls (5% vs 19%, P = .02), and overall survival was superior at 4 years (71% vs 56%, P = .05). At 2 years from transplantation, the B-cell activating factor/B-cell ratio was significantly higher in subjects who developed chronic GVHD in comparison with those without chronic GVHD (P = .039). Rituximab can prevent systemic corticosteroid-requiring chronic GVHD after peripheral blood stem cell transplantation and should be tested in a prospective randomized trial.

Trial registration: ClinicalTrials.gov NCT00379587.

Figures

Figure 1

Chronic GVHD incidence. (A) Overall incidence of chronic GVHD. Dashed line, incidence of all chronic GVHD; solid line, incidence of corticosteroid-requiring chronic GVHD. (B) Incidence of chronic GVHD stratified by donor type. Dotted line, incidence of all chronic GVHD, matched related donors; solid line, incidence of corticosteroid-requiring chronic GVHD, matched related donors; dot-dash line, incidence of all chronic GVHD, matched unrelated donors; dashed line, incidence of corticosteroid-requiring chronic GVHD, matched unrelated donors.

Figure 2

Immunophenotypic outcomes. Bar graph shows median BAFF levels. Open bar, no chronic GVHD; shaded bar, chronic GVHD. Line graph shows median B-cell numbers. Dashed line, chronic GVHD; solid line, no chronic GVHD.

Figure 3

Comparison of rituximab-treated cases and controls. (A) Incidence of corticosteroid-requiring chronic GVHD. Solid line, incidence of corticosteroid-requiring chronic GVHD, rituximab-treated cases; dashed line, incidence of corticosteroid-requiring chronic GVHD, untreated controls. (B) Nonrelapse mortality and disease recurrence. Dotted line, incidence of relapse, rituximab-treated cases; solid line, incidence of nonrelapse mortality, rituximab-treated cases; dot-dash line, incidence of relapse, untreated controls; dashed line, of nonrelapse mortality, untreated controls. (C) Overall survival. Solid line, rituximab-treated cases; dashed, untreated controls.