Efficacy of waitlist desensitization for lung candidates is limited by antibody rebound

HLA antibodies remain a barrier to lung transplantation due to the risk of antibody-mediated rejection (AMR). Desensitization is an option to lower antibody levels and increase access to transplant by reducing risk of AMR. However, concerns remain regarding the efficacy, durability, and risks of administering this treatment while waiting for deceased donor offers. We performed longitudinal antibody assessments for 15 highly sensitized lung candidates undergoing desensitization with plasmapheresis-based treatment protocols. Of the 14 patients transplanted, a significant decrease in overall antibody level was observed in the 2 of 4 patients transplanted within 15 days of the end of their first treatment. Conversely, of the 10 who were transplanted more than 15 days after first treatment, 7 patients rebounded to pre-treatment levels or higher within 3-4 weeks. For the 3 patients in this group who showed a durable decrease, this effect did not manifest until months following treatment. When comparing outcomes for the desensitization cohort against a control group that received treatment post-transplant, no significant differences in survival or acute rejection were observed. These results demonstrate that while plasmapheresis-based waitlist desensitization can effectively remove or reduce the level of HLA antibodies, rebound limits its effectiveness for most patients. To promote successful outcomes, pre-transplant therapy should be targeted to candidates with high lung composite allocation scores likely to be transplanted within the first week after treatment, while aggressive post-transplant immunosuppression may be a safer approach for most highly sensitized patients.