80 Can Monotherapy after One Year Post-Transplant Be Effective without Increasing the Risk of Acute Cellular Rejection?

Abstract

Purpose Multidrug immunosuppression is traditionally implemented to prevent acute cellular rejection (ACR) in cardiac transplant patients despite toxicities. Monotherapy, in contrast, raises concerns of higher risk of immune activation and ACR. We used noninvasive molecular diagnostic testing (MDT) with gene expression profiling to determine if cardiac transplant patients receiving monotherapy with a single calcineurin inhibitor were at greater risk of immune activation and ACR versus those on multi-drug immunosuppression. Methods and Materials 162 patients at least one year post-transplant underwent MDT. 47 (29%) patients were on monotherapy consisting of a single calcineurin inhibitor (CNI), either cyclosporine or tacrolimus. 115 patients were on multi-drug immunosuppression consisting of various combinations of CNI, antiproliferative agents, corticosteroids, and m-TOR inhibitors. Average (±SD) MDT scores were calculated for each group. Results An MDT threshold score of >34 provides a negative predictive value of 98.2 percent that 2R or greater ACR is absent in patients who are at least one year post-transplant. Mean (±SD) MDT scores in the monotherapy group were 28.44±4.62 compared to 29.11±4.08 in the multi-drug immunosuppression group. There was no significant difference in mean MDT scores between the groups (p=.3611). There was no difference in the incidence of 2R or greater ACR between patients on monotherapy and multi-drug immunosuppressive therapy (p=0.18). From the study period of 2005-2010, one patient on monotherapy versus eight patients on multi-drug therapy had 2R ACR. Conclusions 29% of patients more than one year post-transplant were safely managed on monotherapy using MDT. There were no significant differences between the average MDT scores for patients on monotherapy versus multi-drug immunosuppression. Monotherapy did not put patients at increased risk of ACR but facilitated minimization of immunosuppression, potentially improving patient compliance and decreasing risk of adverse side effects.