S1836 Effect of Mammalian Target of Rapamycin (mTOR) Inhibitor Everolimus Upon Skin and Other Malignancy Following Liver Transplantation

Introduction: Malignancy after solid organ transplant especially skin cancers is common phenomenon. Some case reports and small single center studies highlight various antioncogenic effects of mammalian target of rapamycin (mTOR) inhibitor class of immunosuppressants especially everolimus. This study aims to assess the incidence of post transplant skin malignancy and outcomes among liver transplant recipients on everolimus. Methods: A retrospective chart review of liver transplant recipients transplanted at a large tertiary center between 1/2015-12/2019 was conducted. Patients were split into 3 groups: not on everolimus post transplant (group 1), started on everolimus within 1 year of transplant and discontinued before 3 years (group 2) and on everolimus for at least 3 consecutive years (group 3). Demographic data including age and gender were collected with primary outcome assessing the incidence of skin cancer post transplant. Secondary outcomes assessed other post transplant malignancies including non-hepatic gastrointestinal malignancy, transplant rejection and death. Results: Among 381 liver transplant recipients, 67% were in group 1 (n=257), 15% in group 2 (n=59), 17% in group 3 (n=65). 25 patients in group 1 (9.7%), 4 in group 2 (6.8%) and 6 (9.2%) in group 3 developed some skin malignancy with squamous cell carcinoma the most common among all 3 groups (group 1 vs 3, P =0.835; group 2 vs 3, P =0.513). 26 patients in group 1 (10.1%), 6 in group 2 (6.8%) and 5 (7.7%) developed some other type of malignancy, and among other malignancies, hematologic was most common in group 1 (n=6, 23%) and non-hepatic gastrointestinal was most common in group 2 (n=4, 67%) and 3 (n=4, 80%). There was no significant difference in incidence of skin malignancy (group 1 vs 3, P = 0.835; group 2 vs 3, P =0.513), death (group 1 vs 3, P = 0.502; group 2 vs 3, P =0.611) or transplant rejection among the 3 groups (group 1 vs 3, P = 0.305; group 2 vs 3, P =0.066). Conclusion: Our data demonstrates everolimus did not have a protective effect against skin malignancy, other post transplant malignancies, transplant rejection or mortality in liver transplant patients. The data demonstrated that the duration of evrolimus therapy also had no effect on these variables. Whether these study findings were related to short duration of therapy or to a small sample size is unclear. Further investigations are warranted over a longer period of time and with other mTOR agents (see Table 1). Table 1. - Group demographics and results Group 1: no everolimus use Group 2: everolimus within 1 year of transplant but less than 3 years Group 3: everolimus use 3 consecutive years post transplant Total number of patients (n=) 257 59 65 1. Average Age (yrs) 56.6 57.7 57.9 2. Sex a) Males 158 (61.4%) 46 (78%) 47 (72.3%) b) Females 99 (38.5%) 13 (22%) 18 (27.7%) 3.Presence of HCC at transplant 34 (13.2%) 23 (38.9%) 23 (35.3%) 4. Skin cancer post transplant 25 (9.73%) 4 (6.8%) 6 (9.2%) a) Squamous cell carcinoma 15 (60%) 3 (75) 3 (50%) b) Basal Cell carcinoma 8 (32%) 1 (25%) 3 (50%) c) Melanoma 1 (4%) - - d) Primary Sebaceous carcinoma 1 (4%) - - 5. Other post transplant malignancy 26 (10.1%) 6 (10.1%) 5 (7.7%) a) Hematologic 6 (23%) - - b) Genitourinary (bladder/kidney, prostate) 5 (19.2%) - - c) Nonhepatic gastrointestinal (pancreas, colon, ect) 5 (19.2%) 4 (67%) 4 (80%) d) Breast 2 (7.7%) - - e) Gynecologic 3 (11.5%) - - f) Lung 3 (11.5%) - - g) HEENT 1 (3.8%) - - h) Other - - 1 (20%) 6) Transplant rejection 85 (33.1%) 13 (22%) 22 (33.8%) 7) Mortality 48 (18.7%) 16 (27.1%) 13 (20%)