Service de Transplantation Pulmonaire, Hôpital Foch, Suresnes, France.
Service de Biostatistique, Hôpital Foch, Suresnes, France.
PLoS One. 2023 Mar 15;18(3):e0281492. doi: 10.1371/journal.pone.0281492. eCollection 2023.
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.
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).
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).
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.
钙调磷酸酶抑制剂(CNI)仍然是肺移植(LTx)后维持免疫抑制(IS)的基石,尽管可能会发生与 CNI 相关的危及生命的毒性作用。巴利昔单抗是一种新型免疫抑制剂,可阻断 T 细胞共刺激途径,已被批准用于替代肾移植中的 CNI。在 LTx 中,仅有少数关于巴利昔单抗转换为无 CNI 或 CNI 节省 IS 治疗的报告。
我们回顾了一组 10 名 LTx 受者,他们在 LTx 后第一年(n = 7)或第一年之后转换为无 CNI 的巴利昔单抗 IS 方案,或巴利昔单抗/低剂量 CNI 联合方案(n = 3)。
9 例患者因严重肾功能衰竭而使用巴利昔单抗,1 例患者因先前的其他 IS 相关毒性而使用。开始使用巴利昔单抗后 6 个月和最后一次随访时,估算肾小球滤过率(eGFR)显著改善(p = 0.006 和 p = 0.002)。无 CNI 的巴利昔单抗为基础的 IS(n = 4/7)的患者中,复发性和/或严重急性细胞排斥反应(ACR)的发生率较高。9 例接受巴利昔单抗 IS 的患者中,有 2 例发生慢性移植物功能障碍。由于复发性/严重 ACR(n = 3)、复发性机会性感染(n = 1)、中心修改政策(n = 1)或其他原因(n = 1),有 6 例患者停止使用巴利昔单抗。
本系列中,早期转换为无 CNI 的巴利昔单抗为基础的 IS 改善了肾功能,但复发性 ACR 的发生率较高,包括危及生命的发作。需要进一步研究以更好地确定其在 LTx 后的适应证,可能需要使用 CNI 节省的巴利昔单抗等免疫风险较低的 IS 方案。