European multicentre heart transplant study investigating the effectiveness and safety of extracorporeal photopheresis in a real-world setting
Markus Johannes Barten1, Balazs Sax2, Simon Schopka3, Cristiano Amarelli4, Eric Epailly5, Tímea Teszák2, Johannes Gökler6, Benedetta Natali7, Julia Theil8, Kathrin Borchert8, Andreas Zuckermann6.
1Department of Cardiovascular Surgery, University Heart and Vascular Center Hamburg, Hamburg, Germany; 2Heart and Vascular Center, Semmelweis University, Budapest, Hungary; 3Department of Cardiothoracic Surgery, University Medical Center, Regensburg, Germany; 4Department of Cardiovascular Surgery and Transplant, Azienda dei Colli, Monaldi Hospital, Naples, Italy; 5Department of Cardiovascular Surgery, University Hospital of Strasbourg, Strasbourg, France; 6Department of Cardiac Surgery, Medical University of Vienna, Vienna, Austria; 7Department of Cardiac Surgery, Siena University Hospital, Siena, Italy; 8EU Real World Evidence, Xcenda GmbH, Hannover, Germany
Introduction: Extracorporeal photopheresis (ECP) is recommended as an adjunctive therapy in prevention and treatment of acute cellular rejection (ACR) after heart transplantation (HTx) by a number of different clinical societies. However, these recommendations are based on studies conducted over 15 years ago. In clinical practice, ECP is also used to treat antibody mediated rejection (AMR), to prevent rejection in patients at high risk of transplant rejection, or to reduce immunosuppression. The aim of this study was to describe the real-world use of ECP in the modern era of HTx and to assess the effectiveness and safety of ECP.
Method: Seven transplant centres located in five European countries participated in this retrospective, explorative, single-arm chart review study. Heart transplant patients who started ECP in 2015 or later were included in the study and were followed from HTx up to two years after the last ECP treatment. Data have been extracted from the medical charts covering patient characteristics, reasons for ECP treatment, schedule and duration of ECP treatment, concomitant immunosuppressive medication, clinical outcomes (e.g., graft function, rejections, and survival) as well as treatment-related complications and safety.
Results: Overall, 105 heart transplant patients treated with ECP were enrolled. Mean age of patients was 48 years and 70% were male. The main reasons to start ECP were ACR (n=37, 35%), AMR (n=16, 15%), mixed rejection (n=19, 18%), and prevention of rejection (n=33, 31%). Median time from HTx to start of ECP was 359 days. At time of analysis, 58 patients (55%) had completed ECP and in 47 patients (45%), treatment was ongoing. On average, 37 ECP treatments per patient were performed over a mean duration of 13 months. In 97% of patients who completed ECP, graft function was stable at the end of ECP (measured mainly by echocardiography). Of the 72 patients in the rejection groups, 31 had a biopsy at start of ECP and at the end of study period and 27 (87%) showed an improvement of ISHLT classification of ACR or AMR. In the prevention of rejection group, 27 of the 33 patients (82%) remained free from any rejection after starting ECP despite patients considered as being at high risk of rejection or having reduced immunosuppression. For 57% (n=33) of patients who completed ECP (n=58), the main reason for stopping was positive response to treatment. Overall survival among the included 105 patients was 95% over a mean follow-up of two years from start of ECP. Five patients died, three with a functioning graft. No deaths were related to ECP. In total, 18 patients (17%) had an ECP-related safety event, of which 13 patients (12%) experienced complications with venous access.
Conclusion: The results of this largest European ECP study in HTx indicate that ECP is a safe and effective treatment not only for ACR but is also an option for AMR, mixed rejection, and prevention of rejection.
