Objective: The complex pathogenesis of relapsed and refractory (R/R) immune thrombocytopenia (ITP) contributes to the varied efficacy and tolerability of current treatment regimens. Rapamycin, an immunomodulatory agent, was originally used in the prevention of organ rejection after organ transplantation. Additional evidence now shows that rapamycin can successfully treat R/R ITP. Here, we summarize recent clinical progress on the role and potential mechanism of rapamycin in the treatment of ITP.
Methods: PubMed, Web of Science and CNKI database were searched to identify eligible studies, and the clinical data and preclinical studies on the use of mTOR inhibitors in ITP treatment were reviewed. The key results (efficacy and safety) of the most recent clinical reports were summarized.
Results summarized: Case series provide evidence of the effectiveness and tolerable safety profile of rapamycin in ITP, including primary and some secondary ITP. Mechanistic explorations indicate that rapamycin can regulate immune cell subsets (Th1, Th2, Th17, Treg, Breg, MDSC, etc.), modulate cytokine secretion (IL-6, IL-10, TGF-β, BAFF, etc.) and promote platelet autophagy.
Conclusions: Emerging clinical data and basic studies suggest that rapamycin, as a multifaceted regulator, could provide a new promising option for the therapy of ITP. Additional research is needed to identify those patients which may benefit the most, as well as therapeutic regimens with which rapamycin may be combined.
Keywords: ITP; Rapamycin; adverse effects; autophagy; immune tolerance.