Conversion From Calcineurin Inhibitors to Everolimus With Low-Dose Cyclosporine in Renal Transplant Recipients With Squamous Cell Carcinoma of the Skin

Abstract

Squamous cell carcinoma of the skin (SCC) is the most frequent cancer in renal transplant recipients. Conversion to mammalian target of rapamycin inhibitors after diagnosis of SCC may reduce the incidence of recurrence of skin cancer. This retrospective study evaluated the outcome of renal transplant recipients followed by the Renal Unit with posttransplant diagnosis of SCC treated with conversion from calcineurin inhibitors (CNIs) to Everolimus (EVR) associated with low-dose cyclosporine. Eleven patients developed SCC at a median time from renal transplantation of 107 months (range 36 -264). Five patients with creatinine clearance (CCl) below 40 mL/min before conversion developed end stage renal disease (two cases) or further deterioration of renal function (two cases); only one patient in this group maintained a stable renal function. The remaining six patients with a CC1 greater than 40 mL/min and proteinuria below 0.8 g/24 hours maintained a stable renal function after conversion to EVR at a median follow-up of 22 months (range 15-75). Conversion from CNIs to EVR has been proven safe, effective, and associated with low recurrence of SCC in patients with a CCl Ͼ40 mL/min. In the case of preexisting deterioration of renal function or significant proteinuria, conversion to EVR should be carefully evaluated. T HE INCIDENCE OF nonmelanoma skin cancers(NMSC) increases with time after transplantation and varies from 5% to 60% among different geographic areas and according to the time after transplantation. Mammalian target of rapamycin (m-TOR) signaling has an important role in development of cancer and is a critical pathway for several growth factors. 1 Many clinical trials demonstrated that m-TOR inhibitors (m-TORi) have been associated with a reduced incidence of SCC particularly in patients converted from a calcineurin inhibitors (CNI) immunosuppressive regimen.

Everolimus and Malignancy after Solid Organ Transplantation: A Clinical Update

“…The evidence relating to switch to sirolimus following diagnosis of NMSC is more extensive than for everolimus [64], but data is accumulating regarding intervention with everolimus. Caroti et al have described a series of eleven kidney transplant patients who developed SCC at a median of 107 months after transplant [65]. The lesions were surgically excised and patients were switched to everolimus with low-dose cyclosporine (CsA).…”

Everolimus immunosuppression in kidney transplantation: What is the optimal strategy?

“…As seen in studies of pre-emptive conversion to everolimus, a shorter time post-transplant was associated with greater renal benefit [52] and patients with very poor baseline renal function tended to progress to end-stage renal disease [48].…”

“…The literature includes a number of single-center reports from small series of maintenance kidney transplant patients who were switched from CNI therapy to everolimus in response to declining renal function [45,46], malignant neoplasms or nonmelanoma skin cancer [47][48][49][50] or, more frequently, a mixture of indications but primarily renal deterioration or malignancy [51][52][53][54]. Studies of cohorts switched due to renal causes or for mixed reasons have consistently shown a significant improvement in renal function over follow-up periods ranging from six months to two years [45,46,[51][52][53][54].…”

“…Published cases of conversion from CNI therapy to everolimus in response to malignancy describe a variety of tumor types with varying surgical and adjunctive interventions, and have generally concluded that conversion is a valid therapeutic approach which helps to control disease progression [47][48][49][50].…”

The role of mammalian target of rapamycin inhibitors in the management of post‐transplant malignancy

“…However, at one yr, conversion to sirolimus was associated with a significant risk reduction both in all patients and those with only a single previous SCC (Table ). While randomized data are not yet available for everolimus, a low recurrence rate (two of 11 patients) was reported in a retrospective study of kidney transplant recipients who were converted to everolimus plus low‐dose cyclosporine after developing SCC of the skin in the post‐transplant period .…”