Complement as the enabler of carfilzomib-induced thrombotic microangiopathy

Carfilzomib has been associated with the development of thrombotic microangiopathy (TMA) in relapsed/refractory multiple myeloma patients, a severe disease with no currently available aetiological treatment. We evaluated the potential role of terminal complement pathway in four patients with carfilzomib-induced TMA. Membrane attack complex (C5b-9) deposition on endothelial cells in culture exposed to plasma from patients during the acute phase of the disease suggests complement overactivation as a mechanism of potential endothelial damage in three out of four patients. If confirmed in larger cohorts, C5b-9 evaluation will allow early identification of patients who could benefit from complement blockade and treatment monitoring.
Keywords: C5b-9 deposits; carfilzomib; drug-induced thrombotic microangiopathy; eculizumab; endothelial cells.

Reference
Blasco, M., Martínez‐Roca, A., Rodríguez‐Lobato, L. G., Garcia‐Herrera, A., Rosiñol, L., Castro, P., ... & Palomo, M. (2021). Complement as the enabler of carfilzomib‐induced thrombotic microangiopathy. British Journal of Haematology, 193(1), 181-187.

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