Belatacept-based immunosuppression: A calcineurin inhibitor-sparing regimen in heart transplant recipients

Launay, Manon; Guitard, Joëlle; Dorent, Richard; Prevot, Yoann; Prion, Florent; Beaumont, L.; Kably, Benjamin; Lécuyer, Lucien; Billaud, Éliane; Guillemain, R.

doi:10.1111/ajt.15584

Cited by 25 publications

(26 citation statements)

References 19 publications

(31 reference statements)

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“…The CNI avoidance strategy of early conversion to mammalian target of rapamycin (mTOR) inhibitor-based therapy has demonstrated efficacy in preserving renal function, 25 but is suboptimal and limited by the adverse outcomes characteristic of the mTOR inhibitor class (eg, pneumonitis, wound complications, metabolic toxicities). Successful posttransplant conversion to belatacept in nonrenal solid organ transplantation has been previously reported, 26 , 27 but very few instances have been observed in liver transplant recipients. The largest experience in liver transplantation consisted of the successful use of belatacept as a temporary bridge to renal recovery in 7 recipients with hepatitis C, 28 but the duration of belatacept treatment was short, ranging from 19 to 89 d and all patients were converted back to CNIs.…”

Section: Discussionmentioning

confidence: 99%

Belatacept Conversion in Kidney After Liver Transplantation

Cristea

Karadkhele

Kitchens

et al. 2021

Transplantation Direct

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Background. Costimulatory blockade with belatacept has demonstrated long-term benefits in renal transplantation, but de novo use in liver transplant recipients has resulted in increased rejection, graft loss, and death. However, belatacept conversion as a calcineurin inhibitor (CNI) avoidance strategy has not been studied and may be of benefit in liver transplantation where CNI-induced renal dysfunction and toxicity are barriers to improved outcomes. Methods. Using clinical data extracted from our institutional medical record, we report on 8 patients who underwent kidney after liver transplantation and were treated with belatacept-based immunosuppression and transient CNI therapy. Results. All patients tolerated belatacept therapy without any patient deaths or graft losses. No episodes of rejection, de novo donor-specific antibody formation, or major systemic infections were observed, and all patients demonstrated preserved liver and excellent renal allograft function. Patients received belatacept for a median duration of 13.2 mo, and at a median follow-up of 15.9 mo post–kidney transplant, 6 of 8 patients continued on belatacept with 3 completely off and 3 poised to transition off CNI. Conclusions. These findings are the first evidence that in liver transplant recipients requiring subsequent kidney transplantation, belatacept-based therapy can potentially facilitate CNI-free maintenance immunosuppression. This supports the possibility of belatacept conversion in stand-alone liver transplant recipients as a viable method of CNI avoidance.

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Section: Discussionmentioning

confidence: 99%

Belatacept Conversion in Kidney After Liver Transplantation

Cristea

Karadkhele

Kitchens

et al. 2021

Transplantation Direct

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“…CTLA4Ig costimulatory blockade is currently widely used in clinical organ transplantation (45)(46)(47)(48). Recent long-term clinical trials in kidney transplant patients have shown improved graft function, better cardiovascular/metabolic risk profile and similar patient and graft survival when compared to CNIs.…”

Section: Discussionmentioning

confidence: 99%

Targeting Metabolism as a Platform for Inducing Allograft Tolerance in the Absence of Long-Term Immunosuppression

Cheng

Lee

et al. 2020

Front. Immunol.

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Transplant tolerance in the absence of long-term immunosuppression has been an elusive goal for solid organ transplantation. Recently, it has become clear that metabolic reprogramming plays a critical role in promoting T cell activation, differentiation, and function. Targeting metabolism can preferentially inhibit T cell effector generation while simultaneously promoting the generation of T regulatory cells. We hypothesized that costimulatory blockade with CTLA4Ig in combination with targeting T cell metabolism might provide a novel platform to promote the induction of transplant tolerance.

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“…In a multicenter retrospective non-comparative cohort study of 40 heart transplant recipients in France switched from CNI to belatacept, mainly due to impaired renal function on CNI, Launay et al ( 34 ) found that belatacept was associated with a high rate discontinuation and adverse effects. At the end of follow-up, 4/40 (10%) of patients had died (2 of fatal rejection, 1 of invasive infection, 1 of non-compliance).…”

Section: Non-randomized Studiesmentioning

confidence: 99%

Belatacept in Kidney Transplantation: What Are the True Benefits? A Systematic Review

Lombardi

François

2022

Front. Med.

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The current gold standard to prevent allograft rejection for maintenance immunosuppression in kidney transplantation currently consists in glucocorticoids, an antiproliferative agent and a calcineurin inhibitor (CNI), with better outcome for tacrolimus than cyclosporin. Although, CNI drastically improved early graft survival, so far, CNI have failed to significantly improve long-term survival mainly because of nephrotoxicity. In addition, CNI carry several other side effects such as an increased risk for cardiovascular events and for diabetes mellitus. Therefore, seeking alternatives to CNI remains of paramount importance in kidney transplantation. Belatacept is a fusion protein composed of the human IgG1 Fc fragment linked to the modified extracellular domain of cytotoxic T lymphocyte–associated antigen 4. In kidney transplant recipients, pivotal phase III randomized studies suggested clinical benefits of belatacept as an initial maintenance regimen, as compared with cyclosporine, mainly on kidney function. Recently, a randomized study also suggested a clinical benefit on renal function of a conversion from a CNI-based to a belatacept-based maintenance regimen in patients. However, conversion from CNIs to belatacept is probably associated with an increased risk of biopsy-proven acute rejection and should prompt close clinical surveillance. On the other hand, other studies suggest a decrease in de novo humoral transplant immunization. Belatacept is probably associated with an increase in both risk and severity of some infectious diseases, including EBV-linked post-transplantation lymphoproliferative disorders, and with a decreased response to vaccines. Most studies on belatacept are observational, retrospective, and non-comparative. Consequently, high-quality data about the safety and efficacy profile of belatacept, as compared with the current gold standard for maintenance regimens (tacrolimus-based), is uncertain. Our review will therefore focus on the most recent published data aiming at evaluating the evidence-based or the “true” benefits and risks of belatacept-based regimens in kidney transplantation.

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Belatacept-based immunosuppression: A calcineurin inhibitor-sparing regimen in heart transplant recipients

Cited by 25 publications

References 19 publications

Belatacept Conversion in Kidney After Liver Transplantation

Belatacept Conversion in Kidney After Liver Transplantation

Targeting Metabolism as a Platform for Inducing Allograft Tolerance in the Absence of Long-Term Immunosuppression

Belatacept in Kidney Transplantation: What Are the True Benefits? A Systematic Review

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