Assessment of Carfilzomib Treatment Response in Lung Transplant Recipients with Antibody-mediated Rejection

Data supporting the use of carfilzomib (CFZ) for treatment of antibody-mediated rejection (AMR) in lung transplantation in combination with plasmapheresis and intravenous immunoglobulin suggest positive outcomes through donor-specific antibody (DSA) depletion or conversion to noncomplement-activating antibodies. Herein, we describe our center's experience treating AMR with CFZ.

Methods: All patients treated with CFZ for AMR from 2014 to 2019 were included. The primary outcome was a positive response to CFZ was defined as: (1) loss of DSA C1q-fixing ability after last CFZ dose; (2) clearance of de novo DSA; or (3) decrease in de novo DSA mean fluorescence intensity of >3000.

Results: Twenty-eight patients with 31 AMR episodes were treated with CFZ. A positive response was observed in 74.4% of AMR episodes and 82.1% of patients. This response was driven by loss of complement 1q fixation (70.6%), elimination of class I DSAs (78.6%), and reduction in both classes I (median 2815, 79.5% reduction from baseline) and II DSA mean fluorescence intensity (3171, 37.1%).

Conclusions: CFZ shows potential for ameliorating AMR; however, additional studies are needed to define optimal time of administration.