Safety and efficacy of mTOR inhibitors following intestine and multivisceral transplantation

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Conference Proceeding

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Purpose: Review the indications, outcomes and frequency of the use of mTOR inhibitors (mTORs) after intestine (IT) and multivisceral transplantation (MVT) assessed across two transplant centers in the United States. Methods: We evaluated patients receiving everolimus or sirolimus following MVT or IT and compiled retrospective data between 2009-2018 at multiple transplant centers. Results: 22 patients received immunosuppression including an mTOR. Twenty patients were over 18 years. Twelve patients received isolated IT. The most common reason for transplant was short gut syndrome (45%) followed by dysmotility (22%) and neuroendocrine tumor (18%). Mean age at transplant was 46 years (range 22 - 62) in adults and 2.5 in children. 54% patients were started on mTORs beyond 1 year post transplant. Mean time from transplant to initiation of mTOR was 24 months (range 1 - 78). 63.6% received sirolimus and 36.4% received everolimus. Other medications at the time of mTORs initiation included tacrolimus, prednisone, mycophenolate mofetil (MMF) and azathioprine. 18%, 13.6% and 59% of patients on mTORs were able to discontinue MMF, prednisone or reduce tacrolimus respectively. Only one patient was weaned to mTOR as single immunosuppression agent. Reason for mTOR use was renal dysfunction in 59% of cases; of these, only one patient had chronic kidney disease pre transplant. Mean glomerular filtration rate (GFR) prior to mTORs initiation was 40mL/min/1.73sqm. Of those placed on mTORs for renal insufficiency 69.2% had substantial improvement in GFR (defined as increase of 10 points). Nine patients developed some worsening of proteinuria but none were taken off treatment due to this. 27.3% cases developed acute cellular rejection (ACR), 13.6% had cytomegalovirus and two patients died while being on mTOR therapy. mTORs were discontinued in 11/22 cases due to side effects (54.5%), surgeries (18.1%) or ACR (9%). Sirolimus was discontinued in 8/14 (57%), everolimus was discontinued in 3/8 (37.5%). The mean duration of mTORs use in those stopping therapy was 7 months and 18 months in those remaining on therapy. Conclusion: Tolerance of therapy remains challenging with almost a third of those started on mTors unable to tolerate long term treatment due to side effects. If well tolerated, mTORs were generally safe and efficacious following IT and MVT. Further studies with a control group are warranted.





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