Feasibility of Prolonged Calcineurin-Inhibitor Free Immunosuppression After Lung Transplantation - A Retrospective Single Center Analysis

Abstract

<h3>Purpose</h3> Data on Calcineurin-inhibitor (CNI) free Immunosuppression (IS) after lung transplantation is limited to case reports. Various IS agents are reproted as alternative to CNI including proliferation signal inhibitors (PSI), belatacept and induction agents. Aim of this study was to investigate indications and outcome of CNI-free IS in a large LTx cohort. <h3>Methods</h3> A retrospective single center analysis. All patients during in follow-up after LTx with a maintenance IS without CNI were included. Reasons for conversion to CNI-free IS, complications and outcome after conversion were recorded. <h3>Results</h3> Among 2,099 patients in follow-up, 51 (2.4 %) were identified on a CNI-free IS regimen. All 51 patients (29 males, median 56 years and 6.2 years after LTx at conversion) were converted to a triple drug regimen including PSI (n=7 sirolimus, n=44 everolimus), prednisolone and an antimetabolite (n=49 mycophenolate, n=2 azathioprine). Seventeen patients had pre-existing chronic lung allograft dysfunction (CLAD) before conversion. 26 patients (52 %) had malignancy without a curative intention as a reason for conversion from conventional IS with a 1-year survival of 36%. In 11 patients with malignancy and a curative approach survival was 100% and 64% after 1 and 5 years, respectively. 7 of these were re-converted to a CNI-based regimen later. In 14 patients without malignancy, CNI-free IS was used for median 985 days. Most common non-malignant indications were polyneuropathy (n=5) and infections (n=5). 4 of these patients were re-converted to a CNI-based regimen after 97 to 338 days. In patients without malignancy and those with malignancy and curative intention (n=25), survival was 96 and 84%,1 and 5 year after conversion to CNI-free IS respectively. Four of these patients developed CLAD 146 to 1,044 days after conversion. Neuropathy improved in all affected patients. In 31 evaluable patients, median glomerular filtration rate (GFR, CKD-EPI formula) declined from 55 to 51 and 48 ml/min/1.73 m² 6 and 12 months after conversion, respectively. <h3>Conclusion</h3> Prolonged CNI-free IS based on a PSI triple regimen is feasible in selected LTx-patients. Improvement was observed in patients with neurological complications. No significant changes in GFR were noted after conversion. The role of CNI-free IS in a palliative setting of malignancy is unclear.