Alemtuzumab in lung transplantation: an open-label, randomized, prospective single center study.
Jaksch P, Ankersmit J, et al.American Journal of Transplantation 2014; 14(8): 1839-1845
Aims
To evaluate the safety and efficacy of both alemtuzumab and thymoglobulin in patients undergoing lung or combined lung-heart transplants.
Interventions
Patients were administered either alemtuzumab with reduced doses of tacrolimus, steroids and mycophenolate mofetil or thymoglobulin with standard doses of tacrolimus and corticosteroids.
Participants
60 patients undergoing lung or combined lung-heart transplants.
Outcomes
The primary outcome included the glomerular filtration rate. The secondary outcomes were patient and graft survival, recurrent and ongoing rejection episodes, infectious complications and freedom from bronchiolitis obliterans syndrome (BOS).
Follow-up
2 years.
CET Conclusions
In this randomised study comparing Alemtuzumab with allegedly reduced levels of maintenance immunosuppression, (it could be considered a fairly standard dosage of immunosuppression with respect to tacrolimus ), or thymoglobulin induction with what is rightly said to be standard immunosuppression. However there are rather higher trough levels of tacrolimus that are targeted than would be considered usual. Of the 60 recipients of lung transplantation, all but two had bilateral lung transplants. Routine transbronchial biopsies were performed and there was certainly less rejection in the patients who were induced with Alemtuzumab. However all the other outcomes, such as patient survival, graft survival, occurrence of bronchiolitis obliterans syndrome, renal function and infectious complications were the same in both arms of the trial. In particular there was no evidence that renal function was better in the Alemtuzumab arm compared to the thymoglobulin arm but as mentioned above the trough levels of tacrolimus were not really reduced. Despite the reduction of CD4 T lymphocytes which lasted for over a year in the Alemtuzumab arm, there was no increase in opportunistic infections with Alemtuzumab compared to thymoglobulin. The authors also note that there was a trend towards worse survival rates and a higher incidence of bronchiolitis after two years in the Alemtuzumab arm and although they feel that Alemtuzumab is a valuable potent immunosuppressive agent in lung transplantation, they do express some concern about long term safety profiles. It does not seem that the authors have produced convincing evidence that Alemtuzumab should replace thymoglobulin as an induction agent in lung transplantation.
Data analysis
Available case analysis
Trial registration
Not reported.