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

• Published in: Blood Vol. 122; no. 8; pp. 1510 - 1517
• Main Authors: Cutler, Corey, Kim, Haesook T., Bindra, Bhavjot, Sarantopoulos, Stefanie, Ho, Vincent T., Chen, Yi-Bin, Rosenblatt, Jacalyn, McDonough, Sean, Watanaboonyongcharoen, Phandee, Armand, Philippe, Koreth, John, Glotzbecker, Brett, Alyea, Edwin, Blazar, Bruce R., Soiffer, Robert J., Ritz, Jerome, Antin, Joseph H.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 22.08.2013; American Society of Hematology
• Subjects: Adrenal Cortex Hormones - therapeutic use; Adult; Aged; Antibodies, Monoclonal, Murine-Derived - therapeutic use; B-Cell Activating Factor - immunology; B-Cell Activating Factor - metabolism; Disease-Free Survival; Female; Graft vs Host Disease - prevention & control; Humans; Male; Middle Aged; Peripheral Blood Stem Cell Transplantation - adverse effects; Prospective Studies; Rituximab; Transplantation; Transplantation, Homologous; Treatment Outcome; Young Adult
• ISSN: 0006-4971; 1528-0020; 1528-0020
• DOI: 10.1182/blood-2013-04-495895

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/m2 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. This trial was registered at www.clinicaltrials.gov as NCT00379587. •Rituximab prevents steroid-requiring chronic graft-vs-host disease when given after peripheral blood stem cell transplantation.•Overall survival is improved with rituximab after allogeneic peripheral blood stem cell transplantation when compared with a control cohort.