Conversion to belatacept after lung transplantation: Report of 10 cases

Abstract

Background Calcineurin inhibitors (CNIs) remain the cornerstone of maintenance immunosuppression (IS) after lung transplantation (LTx), although CNI-related life-threatening toxic effects may occur. Belatacept, a novel immunosuppressant that blocks a T-cell co-stimulation pathway, is a non-nephrotoxic drug indicated as an alternative to CNIs in kidney Tx. In LTx, there are only a few reports of belatacept conversion as a CNI-free or CNI-sparing IS treatment. Methods We reviewed a series of 10 LTx recipients with conversion to a CNI-free belatacept IS regimen within the first year post-LTx (n = 7) or a belatacept/low-dose CNI combination after the first year (n = 3). Results Use of belatacept was triggered by severe renal failure in 9 patients and under-IS with previous other IS-related toxicities in 1 patient. Mean estimated glomerular filtration rate after starting belatacept significantly improved at 6 months after initiation and at the last-follow-up (p = 0.006, and p = 0.002 respectively). The incidence of recurrent and/or severe acute cellular rejection (ACR) episodes was high in patients with CNI-free belatacept-based IS (n = 4/7). Chronic graft allograft dysfunction developed in 2 of 9 recipients under belatacept IS. Belatacept was stopped in 6 patients because of recurrent/severe ACR (n = 3), recurrent opportunistic infections (n = 1), center modified policy (n = 1), or other cause (n = 1). Conclusion Early conversion to CNI-free belatacept-based IS improved renal function in this series but was counterbalanced by a high incidence of recurrent ACR, including life-threatening episodes. Other studies are needed to better determine the indications for its use after LTx, possibly with lower immunological risk IS regimens, such as CNI-sparing belatacept.

A Pilot Randomized Controlled Trial of De Novo Belatacept-based Immunosuppression After Lung Transplantation

“…Although some case series have reported a potential role for belatacept in lung transplant recipients who are intolerant of calcineurin inhibitors, others have observed severe toxicity that led to treatment discontinuation. 32,33 In combination with our results, this suggests that there is an inherent risk to the use of belatacept in lung transplantation, although predictors of poor outcomes are unknown.…”

A case report of a lung transplant recipient receiving belatacept in combination with low dose tacrolimus complicated by progressive multifocal leukoencephalopathy

“…Nevertheless, using Belatacept without CNI has been associated with an increased incidence of acute cellular rejection. Several studies have reported severe rejection associated with CNI free Belatacept use [ 8 , 9 ]. This observation has been attributed to the lack of inhibition of a key T cell activation pathway by Belatacept compared to CNI based immunosuppression.…”

Transplant Trial Watch

“…It is hard to draw firm conclusions from a small number of patients, but in the absence of any noticeable difference in DSA formation or development of CLAD, this sobering experience would seem to suggest that the risk of de novo belatacept in lung transplant recipients far outweighs any potential theoretical benefit. Other studies have suggested that conversion to belatacept post-transplant might be feasible, but potentially with a higher risk of rejection [ 5 , 6 ]. Numbers are small and more evidence is needed before belatacept-based strategies for lung recipients can be recommended.…”