Frontiers in Medicine (Mar 2020)
Sirolimus as Rescue Therapy for Refractory/Relapsed Immune Thrombocytopenia: Results of a Single-Center, Prospective, Single-Arm Study
- Yimei Feng,
- Yimei Feng,
- Yunshuo Xiao,
- Yunshuo Xiao,
- Hongju Yan,
- Hongju Yan,
- Ping Wang,
- Ping Wang,
- Wen Zhu,
- Wen Zhu,
- Kaniel Cassady,
- Zhongmin Zou,
- Kaifa Wang,
- Ting Chen,
- Ting Chen,
- Yao Quan,
- Yao Quan,
- Zheng Wang,
- Zheng Wang,
- Shijie Yang,
- Shijie Yang,
- Rui Wang,
- Rui Wang,
- Xiaoping Li,
- Xiaoping Li,
- Lei Gao,
- Lei Gao,
- Cheng Zhang,
- Cheng Zhang,
- Yao Liu,
- Yao Liu,
- Peiyan Kong,
- Peiyan Kong,
- Li Gao,
- Li Gao,
- Xi Zhang,
- Xi Zhang
Affiliations
- Yimei Feng
- Medical Center of Hematology, The Xinqiao Hospital of Third Military Medical University, Chongqing, China
- Yimei Feng
- State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University, Chongqing, China
- Yunshuo Xiao
- Medical Center of Hematology, The Xinqiao Hospital of Third Military Medical University, Chongqing, China
- Yunshuo Xiao
- State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University, Chongqing, China
- Hongju Yan
- Medical Center of Hematology, The Xinqiao Hospital of Third Military Medical University, Chongqing, China
- Hongju Yan
- State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University, Chongqing, China
- Ping Wang
- Medical Center of Hematology, The Xinqiao Hospital of Third Military Medical University, Chongqing, China
- Ping Wang
- State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University, Chongqing, China
- Wen Zhu
- Medical Center of Hematology, The Xinqiao Hospital of Third Military Medical University, Chongqing, China
- Wen Zhu
- State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University, Chongqing, China
- Kaniel Cassady
- Irell and Manella Graduate School of Biological Sciences of City of Hope, Duarte, CA, United States
- Zhongmin Zou
- Department of Chemical Defense, School of Preventive Medicine, Third Military Medical University, Chongqing, China
- Kaifa Wang
- School of Mathematics and Statistics, Southwest University, Chongqing, China
- Ting Chen
- Medical Center of Hematology, The Xinqiao Hospital of Third Military Medical University, Chongqing, China
- Ting Chen
- State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University, Chongqing, China
- Yao Quan
- Medical Center of Hematology, The Xinqiao Hospital of Third Military Medical University, Chongqing, China
- Yao Quan
- State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University, Chongqing, China
- Zheng Wang
- Medical Center of Hematology, The Xinqiao Hospital of Third Military Medical University, Chongqing, China
- Zheng Wang
- State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University, Chongqing, China
- Shijie Yang
- Medical Center of Hematology, The Xinqiao Hospital of Third Military Medical University, Chongqing, China
- Shijie Yang
- State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University, Chongqing, China
- Rui Wang
- Medical Center of Hematology, The Xinqiao Hospital of Third Military Medical University, Chongqing, China
- Rui Wang
- State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University, Chongqing, China
- Xiaoping Li
- Medical Center of Hematology, The Xinqiao Hospital of Third Military Medical University, Chongqing, China
- Xiaoping Li
- State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University, Chongqing, China
- Lei Gao
- Medical Center of Hematology, The Xinqiao Hospital of Third Military Medical University, Chongqing, China
- Lei Gao
- State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University, Chongqing, China
- Cheng Zhang
- Medical Center of Hematology, The Xinqiao Hospital of Third Military Medical University, Chongqing, China
- Cheng Zhang
- State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University, Chongqing, China
- Yao Liu
- Medical Center of Hematology, The Xinqiao Hospital of Third Military Medical University, Chongqing, China
- Yao Liu
- State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University, Chongqing, China
- Peiyan Kong
- Medical Center of Hematology, The Xinqiao Hospital of Third Military Medical University, Chongqing, China
- Peiyan Kong
- State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University, Chongqing, China
- Li Gao
- Medical Center of Hematology, The Xinqiao Hospital of Third Military Medical University, Chongqing, China
- Li Gao
- State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University, Chongqing, China
- Xi Zhang
- Medical Center of Hematology, The Xinqiao Hospital of Third Military Medical University, Chongqing, China
- Xi Zhang
- State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University, Chongqing, China
- DOI
- https://doi.org/10.3389/fmed.2020.00110
- Journal volume & issue
-
Vol. 7
Abstract
Immune thrombocytopenia (ITP) is an autoimmune disease which arises due to self-destruction of circulating platelets. Failure to respond or maintain a response to first-line treatment can lead to refractory/relapsed (R/R) ITP. The mechanism remains complicated and lacks a standard clinical treatment. Sirolimus (SRL) is a mammalian target of rapamycin (mTOR) inhibitor that has been demonstrated to inhibit lymphocyte activity, indicating potential for SRL in treatment of ITP. Activation of the mTOR pathway in autoimmune diseases suggests that SRL might be a useful agent for treating ITP. Accordingly, we initiated an open-label, prospective clinical trial using SRL for patients with R/R ITP (ChiCTR-ONC-17012126). The trial enrolled 86 patients, each dosed with 2–4 mg/day of SRL. By the third month, 40% of patients (34 of 86) achieved complete remission (CR) and 45% of patients (39 of 86) achieved partial remission (PR), whereby establishing an overall response rate (ORR) of 85%. By 6 months of treatment, 41% of patients (32 of 78) achieved CR and 29% of patients (23 of 78) achieved PR, establishing an ORR of 70% without serious side effects. After 12 months follow-up, the ORR remained at 65%. We also found that SRL treatment exhibited higher efficacy in achieving CR in ITP patients who were younger than 40 years old or steroid dependent by univariate analysis. Importantly, in patients who responded, SRL treatment was associated with a reduction in the percentage of Th2, Th17 cells, and increase in the percentage of M-MDSCs and Tregs, indicating that SRL may reestablish peripheral tolerance. Taken together, Sirolimus demonstrated efficacy as a second-line agent for R/R ITP.
Keywords
