Clinical features, treatment, and outcomes of patients with carfilzomib induced thrombotic microangiopathy

Background: Thrombotic microangiopathy (TMA) is associated with carfilzomib, and knowledge of carfilzomibinduced TMA is based mainly on case reports. This study investigated the clinical characteristics of patients with carfilzomib-induced TMA and provided a reference for the rational use of carfilzomib. Methods: Reports of carfilzomib-induced TMA were collected for retrospective analysis by searching the Chinese and English databases from inception to January 31, 2024. Results: Sixty-six patients were included, with a median age of 63 years (range 39, 85). The median time to onset of TMA was 42 days (range 1, 1825) from initial administration, and the median number of cycles was 3 cycles (range 1, 15). Hemolytic anemia was recorded in 64 patients, with a median of 8.3 g/dL (range 4.6, 13). Sixtythree patients had thrombocytopenia with a median of 18 x 10 9 /L (range 1, 139). The median value of increased LDH was 1192 IU/L (range 141, 5378). ADAMTS13 activity was normal in 41 (62.1 %) of the 42 patients. Mutations were found in 9 (13.6 %) of the 15 patients. Fifty-seven patients achieved a clinical response after discontinuing carfilzomib and receiving therapeutic plasma exchange (53.0 %), eculizumab (24.2 %), or hemodialysis (39.4 %). Conclusion: Carfilzomib-induced TMA is an important adverse event that should be considered in patients receiving carfilzomib for multiple myeloma with anemia, thrombocytopenia, and acute kidney injury. Withdrawal of carfilzomib and treatment with eculizumab have proven successful in some patients.