Bortezomib in Relapsed/Refractory Autoimmune-Mediated Thrombotic Thrombocytopenic Purpura: A Single-Center Case Series and Systematic Review

Plasma cell‐directed therapy strategies in immune‐mediated thrombotic thrombocytopenic purpura (iTTP)

“…In the literature, there are 10 cases of iTTP that, despite achieving clinical remission, could not achieve ADAMTS13 activity and received plasma cell-directed therapy. 7,38,39,53,54 In accordance with prior definitions of ADAMTS13 complete and partial remission, 31 among the seven patients treated with bortezomib, ADAMTS13 remission was achieved in five patients (one with partial remission, four with complete remission), while among the three patients treated with daratumumab, complete remission was obtained in two patients, and responses were not achieved in one patient. While the patient in the bortezomib group who achieved partial remission was accompanied by systemic lupus erythematosus, one of the two patients in the bortezomib group who did not achieve remission was accompanied by Crohn's disease, and an ADAMTS13 response was obtained after infliximab.…”

“…In iTTP, plasma cell-directed therapy using bortezomib during exacerbations has been reported in four cases. [36][37][38][39] Among these four patients, ADAMTS13 remission was achieved in three patients, while the ADAMTS13 activity status was not reported in one; however, clinical remission was attained. Caplacizumab was not administered in these four reported cases.…”

“…As ADAMTS13 remission could not be achieved despite using bortezomib, the patient was desensitized to rituximab, and then rituximab was administered, which led to ADAMTS13 remission. 39 Rituximab has been shown to be safe and effective in combination with TPE, especially in refractory and/or relapse patients, and more frequently preemptively prevents exacerbations or relapses. 56 If the aim is to achieve ADAMTS13 remission in iTTP treatment, using rituximab before plasma celldirected therapy may be important for the effectiveness of plasma cell-directed therapy.…”

Prolonged Exposure to Caplacizumab as Rescue Therapy in Refractory Immune Thrombotic Thrombocytopenic Purpura

“…A recent review identified 32 patients reported in the literature and at a single institution who received bortezomib therapy for refractory TTP. 6 ~70% of patients had a complete response; median time to relapse was 7 months, and 6% of patients had adverse events. 6 Caplacizumab induces acquired von Willebrand disease, and consequently, a potential bleeding risk in TTP patients.…”

“…6 ~70% of patients had a complete response; median time to relapse was 7 months, and 6% of patients had adverse events. 6 Caplacizumab induces acquired von Willebrand disease, and consequently, a potential bleeding risk in TTP patients. A recent literature review of the drug's safety profile raised concerns about major bleeding to argue against routine use of caplacizumab to treat immune TTP.…”