Rituximab-based first line treatment for chronic GVHD after allogeneic SCT: results of a phase 2 study

Florent Malard, Myriam Labopin, Ibrahim Yakoub-Agha, Sylvain Chantepie, Thierry Guillaume, Didier Blaise, Reza Tabrizi, Leonardo Magro, Bernard Vanhove, Gilles Blancho, Philippe Moreau, Béatrice Gaugler, Patrice Chevallier and Mohamad Mohty

Key points

  • Addition of rituximab to corticosteroid and cyclosporine A is a safe and effective for first line treatment of cGVHD

  • Resistance of PD-L1hi B cells to anti-CD20 depletion, may lead to the suppression of activated follicular helper T cells and cGVHD control


Chronic graft-versus-host disease (cGVHD) is the main cause of late non-relapse mortality and morbidity after allogeneic stem-cell transplantation (allo-SCT). In order to improve such patients' outcome, we conducted a phase 2, prospective, multicenter trial to test the efficacy of addition of rituximab to corticosteroid and cyclosporine A as first line therapy for newly diagnosed cGVHD after allo-SCT. Twenty-four patients (median age, 47 years) with mild (n=2), moderate (n=7) or severe (n=15) cGVHD were included. All patients received rituximab 375 mg/m2 weekly for 4 weeks, followed in patients with partial response by a second course 1 month later. Twenty of 24 patients (83%) were in response at one year. Furthermore, among 19 evaluable patients, 14 (74%) were off corticosteroids. The estimated one-year overall survival was 83% and the one-year cumulative incidence of non-relapse mortality was 14%. One patient died from progressive multifocal leukoencephalopathy. While PD-L1hi naïve B cells were significantly decreased at diagnosis of cGVHD, they increased after anti-CD20 B cell depletion. In contrast, activated ICOShi PD-1hi circulating follicular helper T cells decreased after rituximab treatment. Overall, addition of rituximab to corticosteroid and cyclosporine A appeared to be safe and effective for first line treatment of cGVHD. Furthermore, our data suggest that this efficacy may be, in part, related to an effect on PD-L1hi B cells and follicular helper T cell. This study was registered at, identifier number: NCT01135641.

  • Submitted May 30, 2017.
  • Accepted August 21, 2017.