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

ABSTRACT

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.

KEYWORDS:

• Basiliximab
• etanercept
• hematopoietic stem cell transplantation
• steroid-refractory acute GVHD

Disclosure of potential conflicts of interest

No potential conflicts of interest were disclosed.

Acknowledgments

We thanks all transplant center physicians who participated in the study.

Funding

This work was funded in part by the Key Project of the National Natural Science Foundation of China (81230014), the National High Technology Research and Development Program of China (2012AA020905), the National Natural Science Foundation of China (81100387, 81170501, 81470309, 81471582, 81670169) and Medical Science and Technology Project of Zhejiang Province (2010KYA075).

Author contributions

Conception and design: Yamin Tan, Haowen Xiao, Yi Luo, and He Huang.

Collection, analysis, and interpretation of the data: Yamin Tan, Haowen Xiao, Yi Luo, Depei Wu, Jianping Lan, Qifa Liu, Kang Yu, Yishan Ye, and He Huang.

Drafting the article: Haowen Xiao and He Huang.

Provision of study materials or patients: 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, and He Huang.

Obtaining funding: Yamin Tan, Haowen Xiao, Yi Luo, and He Huang.