Renal Transplantation Using Belatacept Without Maintenance Steroids or Calcineurin Inhibitors

Abstract

Kidney transplantation remains limited by toxicities of calcineurin inhibitors (CNIs) and steroids. Belatacept is a less toxic CNI alternative, but existing regimens rely on steroids and have higher rejection rates. Experimentally, donor bone marrow and sirolimus promote belatacept’s efficacy. To investigate a belatacept-based regimen without CNIs or steroids, we transplanted recipients of live donor kidneys using alemtuzumab induction, monthly belatacept and daily sirolimus. Patients were randomized 1:1 to receive unfractionated donor bone marrow. After 1 year, patients were allowed to wean from sirolimus. Patients were followed clinically and with surveillance biopsies. Twenty patients were transplanted, all successfully. Mean creatinine (eGFR) was 1.10±0.07mg/dl (89±3.56ml/min) and 1.13±0.07 mg/dl (and 88±3.48 ml/min) at 12- and 36-months, respectively. Excellent results were achieved irrespective of bone marrow infusion. Ten patients elected oral immunosuppressant weaning, seven of whom were maintained rejection-free on monotherapy belatacept. Those failing to wean were successfully maintained on belatacept-based regimens supplemented by oral immunosuppression. Seven patients declined immunosuppressant weaning and three patients were denied weaning for associated medical conditions; all remained rejection-free. Belatacept and sirolimus effectively prevent kidney allograft rejection without CNIs or steroids when used following alemtuzumab induction. Selected, immunologically low-risk patients can be maintained solely on once monthly intravenous belatacept.

Systems analysis uncovers inflammatory Th/Tc17-driven modules during acute GVHD in monkey and human T cells

“…Unlike the hyperacute GVHD cohorts, recipients prophylaxed with combinatorial therapies (either with standard-of-care tacrolimus plus methotrexate [Tac/MTX], or Siro plus CTLA4-Ig [Siro/CTLA4-Ig]) 7,8 successfully suppressed hyperacute GVHD. Thus, in the first several weeks posttransplant, both the Tac/Mtx and Siro/CTLA4-Ig cohorts controlled the clinical symptoms of disease ( Figure 1B-C).…”

Tolerance induction to human stem cell transplants with extension to their differentiated progeny

“…Similarly, lymphocyte depletion with agents such as alemtuzumab, followed by shortterm antibody therapy to guide reconstitution of the repopulating cells could also offer a clinically applicable approach 38 . Moreover, recent advances in developing drug-minimization protocols by the use of alemtuzumab combined with a short period of costimulation blockade via belatacept and mTOR inhibition promote acceptance of renal grafts without impediment to Treg function in man 39 . Nevertheless, the current study focused on the competing role(s) of effector T cells and Treg during tolerance induction to stem cell grafts.…”

Defining a Steroid Withdrawal Protocol in a newly established Kidney Transplantation Unit

“…After a 12 months study the biopsy proven AR rate for belatacept/MMF was 14%; for belatacept/sirolimus this fi gure was 4% and for control TAC/MMF this incidence was 3%. Steroid-free immunosuppression may, therefore, not be achieved through CNI-free protocols [61][62][63].…”