Highly sensitized patients are among the most difficult to transplant and are plagued by early rejection and graft loss. Currently, most immunosuppressive agents are directed towards the T-cell response, and our ability to inhibit or reverse antibody production is limited. During a concurrent session at the ATC, several authors presented data on both new and old concepts in improving transplantation among highly sensitized patients and across ABO barriers.
Drs. Tremblay and Driscoll presented data on carfilzomib (CFZ)–a new irreversible proteasome inhibitor–for desensitization. The investigators gave six patients 12 escalating doses of CFZ followed by three sessions of plasmapheresis. They evaluated antibody reduction by single antigen beads and calculated plasma renin activity (PRA). They also explored a novel endpoint for desensitization, which was the number of donors required to match (DRTM). This was calculated by the formula 1/(1-PRA). In brief, they did see a reduction in antibody, PRA, and a reduction in the number of DRTM. In addition, the treatment was well tolerated. As a separate presentation, the investigators also looked at CD138+ bone marrow plasma cells before and after CFZ treatment. They found a reduction of 72% in plasma cells after treatment. They further looked into the genes of the surviving B cells and discovered upregulation of several genes that seemed to protect the cells from the effects of CFZ. Moving forward, the authors anticipate further studies that will hopefully identify a role for CFZ in highly sensitized patients.
Later that session, Dr. Jordan of Cedars-Sinai presented on the long-term outcomes of patients desensitized with intravenous immunoglobulins (IVIg) and rituximab. His team probably has the most experience using this combination therapy, and he presented long-term follow-up of 514 highly sensitized patients treated with desensitization. Of the 514 patients desensitized, 424 (82%) were eventually transplanted. The investigators then compared the 10-year outcomes of these patients to 821 non-sensitized patients. Impressively, they found no difference between patient and graft survival between the groups. Their data is truly remarkable and argues against the prevailing idea that highly sensitized patients treated with desensitization have worse outcomes than those who are not sensitized.
Another interesting paper presenting a new take on an old idea was from the Hopkins group and looked at ABO incompatible transplantation. Again, current thoughts are that outcomes in ABO-incompatible (ABOi) transplantation is not as good as ABO compatible transplantation. In other words, it’s more expensive but incurs a worse outcome. The Hopkins group challenged this concept by comparing the mortality of patients transplanted with an ABOi living donor versus waiting for a compatible deceased donor. Not surprisingly, they found significant benefits in the ABOi transplant group. Their data suggests a new take on appraising outcomes: that outcomes of what is considered higher risk transplantation should be compared to outcomes on dialysis, not to low-risk compatible living donor transplantation.
Post by Dr. Vinay Nair, AJKD Blog Advisory Board member.