OncoImmunology (Mar 2017)

Combining therapeutic antibodies using basiliximab and etanercept for severe steroid-refractory acute graft-versus-host disease: A multi-center prospective study

  • Yamin Tan,
  • Haowen Xiao,
  • Depei Wu,
  • Yi Luo,
  • Jianping Lan,
  • Qifa Liu,
  • Kang Yu,
  • Jimin Shi,
  • Jingsong He,
  • Weiyan Zheng,
  • Xiaoyu Lai,
  • Yuanyuan Zhu,
  • Kaili Du,
  • Yishan Ye,
  • Yanmin Zhao,
  • Gaofeng Zheng,
  • Yongxian Hu,
  • Xiaoyan Han,
  • Yanlong Zheng,
  • Guoqing Wei,
  • Zhen Cai,
  • He Huang

DOI
https://doi.org/10.1080/2162402X.2016.1277307
Journal volume & issue
Vol. 6, no. 3

Abstract

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Acute graft versus host disease (aGVHD) remains a major problem after allogeneic hematopoietic stem cell transplantation. Standard frontline therapy for aGVHD involves corticosteroids. However, fewer than half of patients have a lasting complete response. The long-term mortality rate of steroid-refractory aGVHD (SR-aGVHD) remains around 70%. To date, no consensus has been reached regarding the optimal salvage treatment for SR-aGVHD. We performed the first prospective, multi-center clinical trial to assess the efficacy and safety of a novel approach to treat severe (grades III–IV) SR-aGVHD with the combination of basiliximab and etanercept. Sixty-five patients with severe SR-aGVHD from six centers were included. The median number of basiliximab infusions was 4 (range 2–11) and of etanercept was 9 (range 2–12). At day 28 after starting the combination treatment, overall response (complete and partial response: CR+PR) to second-line treatment was 90.8% with 75.4% being CR. The incidences of CR per organ were 100%, 73.8%, and 79.7% for skin, liver, and gut involvement, respectively. Patients >30-y old (p = 0.043, RR = 3.169), development of grades III–IV liver aGVHD (p = 0.007, RR = 5.034) and cytomegalovirus (CMV) reactivation (p = 0.035, RR = 4.02) were independent predictors for incomplete response. Combined treatment with basiliximab and etanercept resulted in improved CR to visceral aGVHD and significantly superior 2-y overall survival (54.7% vs. 14.8%, p <0.001) compared with classical salvage treatments. Our data suggest that the combination of basiliximab and etanercept may constitute a promising new treatment option for SR-aGVHD.

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