One of the ATC concurrent sessions was dedicated to novel immunosuppressants. Here is a brief breakdown of the session.
Dr. Muhbacher presented Phase 1 results of a novel anti–C1 inhibitor, TNT009. He presented data in healthy volunteers, which revealed strong ex vivo inhibition of the classic complement cascade with TNT009. The authors will be using this drug in transplant recipients next.
Dr. Lefaucheur later presented data on the use of C1 inhibitor (C1 INH) for treating resistant antibody-mediated rejection. After treatment failure with intravenous immunoglobulins (IVIg), rituximab, and plasmapheresis, six patients were treated with twice weekly C1 INH and IVIg for six months. These patients were compared to 21 historic controls. The treatment group showed an improvement in estimated glomerular filtration rate (GFR) compared to the control group, which experienced a decrease in GFR.
As part of the TASK Pilot Trial (Polyclonal Treg Adoptive Therapy for Control of Subclinical Kidney Transplant Inflammation), Dr. Chandran presented data on the use of polyclonal T regulatory cell (Treg) therapy for subclinical rejection found in protocol biopsies. Peripheral blood Tregs were expanded ex vivo and infused into patients found to have subclinical inflammation on 6-month protocol biopsies. Two patients were treated and showed a decrease in inflammation on follow-up biopsy. Kidney function also remained stable. The CTOT-21 study (Treg Adoptive Therapy in Subclinical Inflammation in Kidney Transplantation) will continue to assess the effect of Treg infusions on subclinical inflammation in a larger population of patients.
Dr. Jordan presented the Cedars Sinai experience in using tocilizumb (TCZ, anti-IL6) for chronic antibody-mediated rejection (cAMR). This was an interesting talk, as cAMR is almost impossible to treat and a frequent cause of kidney transplant failure. The team treated 34 patients with TCZ (3-15 doses) after their standard protocol for treating cAMR, which included IVIg and rituximab. Remarkably, they found a reduction in donor-specific antibody and stabilization in estimated GFR. Of four patients with follow-up biopsies, three showed a dramatic improvement in inflammation and C4d deposition. Glomerular and interstitial fibrosis and tubular atrophy (IFTA) scores did not change. When compared to a separate cohort of 41 patients with cAMR treated without TCZ, they found dramatic improvements in long-term survival with TCZ therapy. Dr. Jordan was very interested in validating these results in other centers or perhaps with a larger multicenter study.
Post by Dr. Vinay Nair, AJKD Blog Advisory Board member.