Bortezomib in relapsed/refractory immune thrombotic thrombocytopenic purpura: A single‐centre retrospective cohort and systematic literature review

Abstract

SummaryImmune thrombotic thrombocytopenic purpura (iTTP) is a rare and life‐threatening haematological condition. Initial treatment involves plasma exchange (PLEX), corticosteroids, caplacizumab and rituximab. In relapsed and refractory cases despite initial treatments, further immune‐modulating therapy includes the proteasome inhibitor, bortezomib. Evidence for bortezomib in this setting is limited to case reports and case series. We report our experience and perform a systematic review of the literature. We identified 21 publications with 28 unique patients in addition to our cohort of eight patients treated with bortezomib. The median age of patients was 44 years (IQR: 27–53) and 69% female. They were usually in an initial, refractory presentation of iTTP where they had received PLEX, corticosteroids, rituximab and another line of therapy. After bortezomib administration, 72% of patients had a complete response, with 85% maintaining a durable response without relapse at the last follow‐up.

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.…”

“…However, in a case of primary iTTP with relapses, bortezomib was applied when rituximab could not be used due to the development of severe anaphylaxis. 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 .…”

“…In iTTP, plasma cell‐directed therapy using bortezomib during exacerbations has been reported in four cases 36–39 . 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.…”