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

Weilun Fang; Wei Sun; Weijin Fang; Shaoli Zhao; Chunjiang Wang

doi:10.1016/j.intimp.2024.112178

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

Int Immunopharmacol. 2024 May 9:134:112178. doi: 10.1016/j.intimp.2024.112178. Online ahead of print.

Authors

Weilun Fang¹, Wei Sun², Weijin Fang², Shaoli Zhao³, Chunjiang Wang⁴

Affiliations

¹ Department of Pharmacy, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China; College of Pharmacy, Changsha Medical University, Changsha, Hunan 410219, China.
² Department of Pharmacy, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China.
³ Department of Endocrinology, The Third Xiangya Hospital, Central South University, China.
⁴ Department of Pharmacy, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China. Electronic address: wongcj@csu.edu.cn.

PMID: 38728883
DOI: 10.1016/j.intimp.2024.112178

Abstract

Background: Thrombotic microangiopathy (TMA) is associated with carfilzomib, and knowledge of carfilzomib-induced 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). Sixty-three patients had thrombocytopenia with a median of 18 × 10⁹/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.

Keywords: Atypical hemolytic uremia syndrome; Carfilzomib; Eculizumab; Therapeutic plasma exchange; Thrombotic microangiopathy.