Off-label use of alemtuzumab, belatacept, and rapamycin in kidney transplantation—Long-term real-world experience

Conventional immunosuppressive regimens in kidney transplantation continue to pose significant challenges, largely due to their reliance on calcineurin inhibitors (CNIs) and corticosteroids. These challenges have driven the search for alternative regimens to minimize toxicity and preserve long-term graft function. In this study, we present real-world data utilizing a CNI-free regimen that makes use of the synergistic effects of costimulation blockade and mTOR inhibition. We retrospectively analyzed 106 kidney recipients from 2016 to 2024 who received alemtuzumab induction, followed by de novo belatacept and sirolimus maintenance therapy (alemtuzumab, belatacept, rapamycin regimen). Patient and graft survival were 100% at 1 year and 96% and 97% respectively, at 5 years. At 3 and 5 years, median glomerular filtration rate was 64 mL/min/1.73 m² (interquartile range 54-75) and 62 mL/min/1.73 m² (interquartile range 54-74), respectively. The rate of rejection in the first year was 6.6%. Ninety-six patients (91%) avoided treatment with CNIs during the follow-up period. Alemtuzumab and belatacept were well tolerated, but 44% of patients discontinued sirolimus, typically due to sirolimus-related side effects remedied with conversion to mycophenolate and prednisone. These results inform and support the study of the alemtuzumab, belatacept, rapamycin protocol, or similar costimulation blockade–based regimens, in pursuit of non–CNI-based therapies for kidney transplant recipients.