Abstract 15858: Does Switching to Proliferation Signal Inhibitors Decrease the Risk of Developing Subsequent Malignancies in Heart Transplant Patients?

Introduction: Malignancy is vast approaching as the leading cause of death late after heart transplantation. It is known that the current immunosuppression regimen consisting of tacrolimus/cyclosporine and mycophenolate is associated with increased risk of cancers. The use of proliferation signal inhibitors (PSI) has been associated with less cancer development particularly in specific tumors. We sought to determine if there is an association of the use of PSI in decreasing overall cancer risk. Methods: Between 2004 and 2008 we assessed 16 heart transplant patients who were placed on PSI and compared cancer development based on conditional survival in the ensuing 5 years to those not on PSI (n=16). Patients were matched according to age, sex, time from transplant, and era. Results: Patients were switched to PSI on an average of 0.9 ± 0.9 years after transplant. Those patients that were placed on PSI had a higher subsequent 5-year actuarial freedom from cancer development compared to those patients not on PSI (100.0% vs 77.7%, p=0.049). These specific cancers included: skin cancer (2), squamous cell cancer (2), auricular carcinoma (1), prostate cancer (1), and cranial meningioma (1). There was no difference in 5-year actuarial freedom from cardiac allograft vasculopathy (CAV) development between the CNI + MMF/AZA and CNI + PSI groups (81.3% vs 72.2%,p=0.683). Conclusions: The use of PSI after heart transplantation appears to confer a protective effect against the development of malignancy. Larger number of patients are needed to confirm these observations.

Abstract 16941: Questioning the efficacy of Proliferation Signal Inhibitors for established Coronary Artery Disease after Heart Transplant

Purpose: Cardiac Allograft Vasculopathy (CAV) is one of the major factors limiting long term survival after heart transplantat (HTx). The use of proliferation signal inhibitors (PSIs) such as everolimus and sirolimus has been found to be effective in the prevention of CAV in multicenter studies. There has been 1 study (Mancini et al) that has suggested the use of Sirolimus can decrease the progression of CAV in patients (Pts) long term after Htx. It is not been evaluated in the current era of Tacrolimus (TAC)/Mycophenolate Mofetil (MMF) whether a switch from MMF to PSIs has such an advantage. Methods: Between 1998 and 2010, we evaluated 26 HTx Pts who had developed CAV according to the new ISHLT CAV nomenclature (CAV1, CAV2, CAV3) and were subsequently switched from TAC/MMF to TAC/PSIs. Pts who were maintained on TAC/MMF were served as 1:1 controls. Outcomes for these Pts included worsening of CAV by category at 3 year, subsequent 3-year survival and subsequent 3-year freedom from non-fatal major adverse cardiac events (NF-MACE: Myocardial Infarction, Congestive Heart Failure, angioplasty, pacemaker/ICD and stroke). Results: There were 26 patients in the switched to PSIs group and 23 patients in the maintained on MMF group. All patients were either CAV 1 or CAV 2 at baseline. The average time to switch to PSIs was 5.3 ± 3.3 years. At 3 year follow up, the percentage of patients who had worsened CAV by category were comparable among the two groups. Subsequent 3-year survival and 3-year freedom from NF-MACE were also comparable among the two groups (see Table). Conclusions: In the current era of TAC/MMF, switch from MMF to PSI for patients with established CAV does not appear to be beneficial in preventing progression of disease. A larger number of patients are needed to confirm this finding.