A Single-center Clinical Trial of Bortezomib in Management of Immune Thrombocytopenia (ITP)
Status:
Unknown status
Trial end date:
2017-12-01
Target enrollment:
Participant gender:
Summary
Primary immune thrombocytopenia (ITP) is a disorder caused by autoantibody-mediated platelet
destruction and decreased platelet production. It has been reported that refractory ITP is
closely related to long-lived plasma cells (PCs), which are resistant to glucocorticoids,
conventional immunosuppressive and cytotoxic drugs, irradiation and B-cell depletion
therapies.
Proteasome inhibition bortezomib is one of the most promising therapeutic approaches to
target PCs, since this strategy has been shown to efficiently eliminate multiple myeloma
cells, that is, transformed PCs. It also has been successfully used in SLE-like mice,
experimental autoimmune MG rats and experimental hemophilia-A mice that develop anti-factor
VIII antibodies in preclinical models by depleting both short-lived and long-lived PCs.
Additionally, treatment with bortezomib resulted in a rapid clinical response in a patient
with refractory thrombotic thrombocytopenic purpura associated with the depletion of
inhibitory autoantibodies against ADAMTS13, a metalloproteinase that cleaves the von
Wille-brand factor, which is produced by plasma cells. Hence, the elimination of autoreactive
PCs by proteasome inhibitors might represent a new treatment strategy for
autoantibody-mediated diseases.
To date, refractory ITP is lacking of effective treatments and these findings encouraged us
to conduct a study of bortezomib in management of ITP with high anti-platelet antibodies
level. Data from this study may provide some idea of bortezomib in the treatment of ITP.