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-L1^hi naive B cells were significantly decreased at diagnosis of cGVHD, they increased after anti-CD20 B-cell depletion. In contrast, activated ICOS^hi PD-1^hi 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-L1^hi B cells and Tfh cells. This study was registered at www.clinicaltrials.gov as identifier NCT01135641.

慢性移植物抗宿主病（cGVHD）是同种异体干细胞移植（allo-SCT）后晚期非复发死亡率和发病率的主要原因。为了改善此类患者的预后，我们进行了一项2期，前瞻性，多中心试验，以测试在皮质类固醇（CSs）和环孢霉素A（CsA）中添加利妥昔单抗作为allo-SCT后新诊断的cGVHD的一线治疗的疗效。纳入了24例轻度（n = 2），中度（n = 7）或重度（n = 15）cGVHD的患者（中位年龄47岁）。所有患者均接受利妥昔单抗375 mg / m ²对于部分缓解的患者，每周一次，持续4周，然后在1个月后，进行第二次疗程。1年后有24例患者中有20例（83％）有反应。此外，在19例可评估患者中，有14例（74％）不使用CS。估计的1年总生存率为83％，1年非复发性死亡率的累积发生率为14％。1例患者死于进行性多灶性白质脑病。虽然PD-L1^喜幼稚B细胞在慢性GVHD的诊断显著下降，它们的抗CD20的B细胞耗竭后增加。相比之下，激活的ICOS ^hi PD-1 ^hi利妥昔单抗治疗后循环T滤泡辅助细胞（Tfh）减少。总体而言，在皮质类固醇和CsA中添加利妥昔单抗对于cGVHD的一线治疗似乎是安全有效的。此外，我们的数据表明，这种功效可能部分与对PD-L1 ^hi B细胞和Tfh细胞的作用有关。该研究已在www.clinicaltrials.gov上注册，标识为NCT01135641。