Abstract Rationale Antibody-mediated rejection (AMR) after lung transplantation is a significant cause of graft failure and mortality. Currently, there are no standardized protocols for AMR treatment. At our institution, we treat definite or severe AMR with graft dysfunction with PLEX+Bortezomib+IVIG, probable AMR with graft dysfunction with PLEX+Rituximab+IVIG, and probable AMR without graft dysfunction with Rituximab+IVIG. We hypothesized that there would be improved clinical outcomes in patients treated with PLEX+Bortezomib+IVIG compared to those treated with PLEX+Rituximab+IVIG, because of targeting antibody-producing plasma cells with bortezomib. Methods We performed a single-center, retrospective observational cohort study. The cohort included 46 episodes of AMR in 35 lung transplant patients treated for AMR over 4 years (2020-2024). We collected data on patient demographics, donor-specific antibodies, mean fluorescence intensity (MFI), complement fixation, and graft dysfunction. The outcomes we collected were death, progressive lung dysfunction characterized by ongoing decline in FEV1 at 3 months after AMR treatment, and resolution of antibody detection. Results In the study cohort, there were 18 episodes of AMR treated with PLEX+Bortezomib+IVIG, 19 treated with PLEX+Rituximab+IVIG, 3 treated with Rituximab+IVIG, and 6 with other regimens. The median time since transplant was 612 days (IQR 128-1359). The majority of donor-specific antibodies were to class II HLA antigens (33 of 45, DQ7 in 14 patients) with no significant differences in MFI between treatment groups. Overall, 28% of patients died, 35% had progressive lung dysfunction, and 35% had stable lung function. In those with stable lung function after treatment, two-thirds had persistence of the donor-specific antibodies. There were no major differences in clinical outcomes by treatment group (Figure). In the group that was treated with PLEX+Bortezomib+IVIG, 8 patients died, 5 had decrease in FEV1 at 3 months, and 5 had stable or improved FEV1. In patients treated with PLEX+Rituximab+IVIG, 5 patients died, 6 had decrease in FEV1 at 3 months, and 8 had stable or improved FEV1. Two out of 3 patients treated with Rituximab+IVIG alone died. MFI, complement fixation, or time since transplant each had no detectable association with treatment outcome. Conclusions In this comparison of treatment regimens for antibody-mediated rejection in lung transplant patients, we found that clinical outcomes were poor with all treatment regimens. Despite our hypothesis that targeting plasma cells with bortezomib would be favorable, this was not supported by data. Further work and randomized clinical trials are needed to better optimize treatments for this devastating complication of lung transplantation. This abstract is funded by: NIH
Ritossa et al. (Fri,) studied this question.