Alemtuzumab induction therapy in kidney transplantation

Abstract

The 3C Study Collaborative Group report a reduction of biopsy-proven acute rejection (BPAR) from 16% with basiliximab to 7% with alemtuzumab in a randomised trial of 852 renal transplant recipients.1Haynes R Harden P et al.3C Study Collaborative GroupAlemtuzumab-base induction treatment versus basilixmab-base induction treatment in kidney transplantation (the 3C Study): a randomised trial.Lancet. 2014; 384: 1684-1690Summary Full Text Full Text PDF PubMed Scopus (99) Google Scholar Despite its rather high rate and standardised detection, BPAR nowadays should no longer guide treatment decisions. Early BPAR without effect on graft function is well known to have no effect on long-term outcomes.2Vereerstraeten P Abramowicz D de Puaw L Kinnaert P Absence of deleterious effect on long-term kidney graft survival of rejection episodes with complete functional recovery.Transplantation. 1997; 63: 1739-1743Crossref PubMed Scopus (70) Google Scholar Hence, for trials of renal transplantation, both the European Medicines Agency and US Food and Drug Administration have suggested use of combined primary endpoints that include patient and graft survival, and graft function besides acute rejection. In this trial, despite the reported advantage of BPAR, graft loss summed to 4% and patient death summed to 3% with alemtuzumab, with graft loss summing to 3% and patient death summing to 1% with basiliximab at 1 year. Therefore, the authors should provide numbers of non-death-censored graft loss (sum of death and graft loss) in both groups (these would theoretically sum to 6·3% [alemtuzumab] vs 4·5% [basiliximab] if only one event is assumed to occur in any given patient). Furthermore, BK virus infection occurred twice as often with alemtuzumab than with basiliximab, and leucopenia was 3·6 times more frequent, both of which might reduce graft survival long term. Some evidence suggests that long-term outcomes might be inferior with alemtuzumab compared with conventional induction treatment.3Ciancio G Gaynor JJ Guerra G et al.Randomized trial of three induction antibodies in kidney transplantation: long-term results.Transplantation. 2014; 97: 1128-1138Crossref PubMed Scopus (31) Google Scholar Finally, clinical use of alemtuzumab might be severely hampered because the drug (MabCampath) has been withdrawn from the market in the European Union since Aug 8, 2012. BKK reports personal fees from Astellas, Bristol-Myers Squibb, Novartis, Chiesi, and Roche outside the submitted work. The other authors declare no competing interests. Alemtuzumab-based induction treatment versus basiliximab-based induction treatment in kidney transplantation (the 3C Study): a randomised trialCompared with standard basiliximab-based treatment, alemtuzumab-based induction therapy followed by reduced CNI and mycophenolate exposure and steroid avoidance reduced the risk of biopsy-proven acute rejection in a broad range of patients receiving a kidney transplant. Long-term follow-up of this trial will assess whether these effects translate into differences in long-term transplant function and survival. Full-Text PDF Alemtuzumab induction therapy in kidney transplantation – Authors' replyThe 3C Study showed that alemtuzumab-based induction treatment compared with standard basiliximab-based induction treatment reduced the risk of biopsy-proven acute rejection by about a half within the first 6 months of transplantation, without any excess infectious or other complications during this period.1 The 3C Study was designed to reliably investigate the long-term effects of alemtuzumab-based induction treatment on outcomes such as graft survival, which previous studies (including those cited by Andrea Berghofen and colleagues)2 have been too small to do. Full-Text PDF