Sirolimus as Rescue Therapy for Refractory/Relapsed Immune Thrombocytopenia: Results of a Single-Center, Prospective, Single-Arm Study
Open Access
- 31 March 2020
- journal article
- research article
- Published by Frontiers Media SA in Frontiers in Medicine
- Vol. 7, 110
- https://doi.org/10.3389/fmed.2020.00110
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.Funding Information
- Natural Science Foundation of Chongqing (cstc2019jcyj-msxmX0273)
- National Natural Science Foundation of China (81400081)
This publication has 31 references indexed in Scilit:
- Cellular immune dysfunction in immune thrombocytopenia (ITP)British Journal of Haematology, 2013
- Effects of Rapamycin Combined with Low Dose Prednisone in Patients with Chronic Immune ThrombocytopeniaJournal of Immunology Research, 2013
- The immunopathogenesis of immune thrombocytopeniaCurrent Opinion in Hematology, 2012
- Eltrombopag for management of chronic immune thrombocytopenia (RAISE): a 6-month, randomised, phase 3 studyThe Lancet, 2011
- The effect of rituximab on humoral and cell mediated immunity and infection in the treatment of autoimmune diseasesBritish Journal of Haematology, 2010
- Elevated profile of Th17, Th1 and Tc1 cells in patients with immune thrombocytopenic purpuraHaematologica, 2009
- Treatment with sirolimus results in complete responses in patients with autoimmune lymphoproliferative syndromeBritish Journal of Haematology, 2009
- Is splenectomy still the gold standard for the treatment of chronic ITP?American Journal of Hematology, 2007
- Three-year health-related quality-of-life outcomes for sirolimus-treated kidney transplant patients after elimination of cyclosporineTransplant International, 2007
- Health-related quality-of-life outcomes of sirolimus-treated kidney transplant patients after elimination of cyclosporine A: results of a 2-year randomized clinical trial1Transplantation, 2003