Alemtuzumab and thrombotic thrombocytopenic purpura: Analysis of an international surveillance database and systematic literature review.

Objectives: Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy associated with severe deficiency in ADAMTS13. ADAMTS13 deficiency may be secondary to absent or dysfunctional protein production due to mutations in the ADAMTS13 gene (congenital TTP) or autoantibody-mediated clearance and/or inhibition (immune-mediated TTP). This autoimmunity may, albeit rarely, occur secondary to certain medications (eg, ticlopidine). Recent case reports have implicated alemtuzumab (LETRADA), a monoclonal antibody that selectively inhibits CD52, as a cause of secondary TTP. We aimed to characterize all reports of TTP potentially associated with alemtuzumab.

Methods: We performed a cross-sectional analysis of the United States Food and Drug Administration's Adverse Event Reporting System (FAERS) database as of 21 November 2024 and systematically reviewed the literature as of 03 September 2024 for all reported cases of secondary TTP potentially associated with alemtuzumab. Patient demographics, therapy indications, associated medications, and outcomes were abstracted.

Results: We identified 49 reports of TTP possibly related to alemtuzumab administration since 01 January 2001 in the FAERS database, 9 of which resulted in death. Most patients (n = 31) were receiving alemtuzumab for multiple sclerosis (MS), while 8 reports were in patients undergoing hematopoietic stem cell transplantation. We identified two additional cases in the literature review in patients receiving alemtuzumab for MS.

Conclusions: In conjunction with studies of the United Kingdom's and European Union's pharmacovigilance databases, these results support the current package insert for alemtuzumab in which TTP is listed as a "warning and precaution". Increased awareness of this possible side effect, and prolonged monitoring, is warranted.