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

Abstract : Chronic graft-versus-host disease (cGVHD) is the main cause of late nonrelapse mortality and morbidity after allogeneic stem cell transplantation (allo-SCT). To improve such patients' outcomes, we conducted a phase 2, prospective, multicenter trial to test the efficacy of the addition of rituximab to corticosteroids (CSs) and cyclosporine A (CsA) 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 by a second course 1 month later for patients with partial response. Twenty of 24 patients (83%) were in response at 1 year. Furthermore, among 19 evaluable patients, 14 (74%) were off CSs. The estimated 1-year overall survival was 83%, and the 1-year cumulative incidence of nonrelapse mortality was 14%. One patient died of progressive multifocal leukoencephalopathy. Although PD-L1hi naive B cells were significantly decreased at diagnosis of cGVHD, they increased after anti-CD20 B-cell depletion. In contrast, activated ICOShi PD-1hi circulating T follicular helper (Tfh) cells decreased after rituximab treatment. Overall, the addition of rituximab to corticosteroid and CsA 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 Tfh cells.
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https://www.hal.inserm.fr/inserm-02155352
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Submitted on : Thursday, June 13, 2019 - 3:03:55 PM
Last modification on : Friday, June 14, 2019 - 1:59:05 AM

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Florent Malard, Myriam Labopin, Ibrahim Yakoub-Agha, Sylvain Chantepie, Thierry Guillaume, et al.. Rituximab-based first-line treatment of cGVHD after allogeneic SCT: results of a phase 2 study. Blood, American Society of Hematology, 2017, 130 (20), pp.2186-2195. ⟨10.1182/blood-2017-05-786137⟩. ⟨inserm-02155352⟩

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