Body: A 33y old female Hispanic patient with a history of congenital heart disease and Fontan associated liver disease was listed for heart/liver transplant. She had a history of multiple surgeries and transfusions and was strongly and broadly sensitized at the time of listing with a cPRA of 100%. Her highly sensitized status, rare HLA type, blood group B, and size limitation due to her small stature prevented her from getting any offers, and desensitization was scheduled. As a first attempt for desensitization, she underwent eight rounds of plasmapheresis with bortezomib treatment, but no decrease in her HLA antibodies was detected. As a second attempt, she was treated with tocilizumab, a humanized monoclonal antibody to IL-6 receptor, however, her HLA antibodies did not show meaningful decrease after five months of treatment. As a third attempt, she received plasmapheresis every other day as well as weekly IVIG, which only had modest effect on her HLA antibodies. As a final attempt for desensitization, the patient consented to receive imlifidase, a Streptococcus derived endopeptidase, after attaining FDA approval for expanded access for an individual patient and expedited institutional IRB approval, given her refractoriness to conventional desensitization therapies. The patient’s HLA avoids, apart from the two strongest of her HLA Class II antibodies were removed from Unet (cPRA of 42%), to allow for offers. After several months, a suitable offer with matching organ size and blood group was accepted. Multiple DSA is shown in Figure 1A. After administration of imlifidase 0.25 mg/kg IV, serial serum samples were tested using single antigen assay (LabScreen, One Lambda/ThermoFisher) starting at 2h post-treatment. A dramatic decrease was detected in all her HLA antibodies at the earliest 2h timepoint (Figure 1B). The patient was transplanted with the heart 18 hours post-imlifidase treatment, followed within a few hours by the liver transplant. To our knowledge, this is the first case of using imlifidase in a heart/liver transplant recipient.
Conclusion: This case shows that imlifidase may be a viable approach for the removal of pre-existing HLA antibodies in highly sensitized transplant candidates who are refractory to conventional desensitization therapies, specifically in the setting of combined heart/liver transplant, providing a window during which they can be transplanted.
