(768) - Proliferation Signal Inhibitors Prevent Donor-Specific Antibody Production in Sensitized Patients after Heart Transplantation

Abstract

Everolimus and sirolimus are proliferation signal inhibitors (PSI) reported to decrease incidence and progression of transplant coronary artery disease, incidence of cardiac rejection, and development of de novo circulating antibodies (Abs) in the 1st year after heart transplant (Htx). Donor-specific Abs (DSA) appear to be a main factor associated with poor outcome in sensitized patients post-Htx. It is not established whether PSIs affect development of DSA in sensitized patients after Htx. Between 2010 and 2014, we evaluated 78 Htx patients (pts) with circulating Abs after Htx. Several were switched from mycophenolate mofetil (MMF) to PSI including everolimus (n=19) or sirolimus (n=11) in combination with a calcineurin inhibitor (CNI). Pts with pre-existing DSA were excluded. Pts were divided into 2 groups: maintenance of MMF use ≥1-year (Group A), and PSI use ≥ 1-year (Group B). Maintenance MMF group was matched to the switch-to-PSI group for time from Htx. Assessment of circulating Abs, including development of de novo DSA at 12 months after initiation of PSI was performed. In addition, 1-year subsequent survival and freedom from subsequent DSA development, cellular rejection, antibody-mediated rejection (AMR) were recorded. Reduction of PRA over 1 year was recorded for both groups. The PSI group compared to the MMF group had significantly greater freedom from de novo DSA development over the course of 1 year (see table). There was no significant difference between study groups in 1-year subsequent survival and 1-year subsequent freedom from cellular rejection and AMR. There was no significant difference with treatment of PSIs for subsequent 12-month Class I Abs levels %PRA (38 ± 37 vs. 33 ± 34, P=0.58) or Class II Abs levels %PRA (19 ± 29 vs. 20 ± 28, p=0.81). The use of PSIs in sensitized Htx pts appears to lower de novo development of subsequent DSA compared to maintenance MMF. Further study is warranted with a larger population.Tabled 1EndpointsGroup A Mycophenolate ≥ 1-Year (N=48)Group B PSI ≥ 1-Year (N=30)P-Value1-Year Subsequent Survival after PSI or MMF Initiation100.0%100.0%1.0001-Year Subsequent Freedom from De Novo Antibody Development after PSI or MMF Initiation86.9%100.0%0.0421-Year Subsequent Freedom from Any Treated Rejection93.8%96.7%0.5721-Year Subsequent Freedom from Acute Cellular Rejection97.9%96.7%0.7431-Year Subsequent Freedom from Antibody-Mediated Rejection97.9%93.2%0.3061-Year Subsequent Freedom from Biopsy Negative Rejection97.9%100.0%0.429 Open table in a new tab