Harland Robert C, Klintmalm Goran, Jensik Stephen, Yang Harold, Bromberg Jonathan, Holman John, Kumar Mysore S A, Santos Vicki, Larson Tami J, Wang Xuegong
Department of Surgery, University of Arizona, Tucson, Arizona.
Department of Transplantation Services, Annette C. and Harold C. Simmons Transplant Institute, Dallas, Texas.
Am J Transplant. 2020 Jan;20(1):159-171. doi: 10.1111/ajt.15591. Epub 2019 Oct 19.
This study assessed the efficacy and safety of the anti-CD40 monoclonal antibody bleselumab (ASKP1240) in de novo kidney transplant recipients over 36 months posttransplant. Transplant recipients were randomized (1:1:1) to standard of care (SoC: 0.1 mg/kg per day immediate-release tacrolimus [IR-TAC]; target minimum blood concentration [C ] 4-11 ng/mL plus 1 g mycophenolate mofetil [MMF] twice daily) or bleselumab (200 mg on days 0/7/14/28/42/56/70/90, and monthly thereafter) plus either MMF or IR-TAC (0.1 mg/kg per day; target C 4-11 ng/mL days 0-30, then 2-5 ng/mL). All received basiliximab induction (20 mg pretransplant and on days 3-5 posttransplant) and corticosteroids. One hundred thirty-eight transplant recipients received ≥1 dose of study drug (SoC [n = 48]; bleselumab + MMF [n = 46]; bleselumab + IR-TAC [n = 44]). For the primary endpoint (incidence of biopsy-proven acute rejection [BPAR] at 6 months), bleselumab + IR-TAC was noninferior to SoC (difference 2.8%; 95% confidence interval [CI] -8.1% to 13.8%), and bleselumab + MMF did not demonstrate noninferiority to SoC (difference 30.7%; 95% CI 15.2%-46.2%). BPAR incidence slightly increased through month 36 in all groups, with bleselumab + IR-TAC continuing to demonstrate noninferiority to SoC. Bleselumab had a favorable benefit-risk ratio. Most treatment-emergent adverse events were as expected for kidney transplant recipients (ClinicalTrials.gov NCT01780844).
本研究评估了抗CD40单克隆抗体布莱昔单抗（ASKP1240）在肾移植受者移植后36个月内的疗效和安全性。将移植受者随机分为三组（1:1:1）：标准治疗组（SoC：每日0.1mg/kg速释他克莫司[IR-TAC]；目标最低血药浓度[C]4-11ng/mL加每日两次1g霉酚酸酯[MMF]）或布莱昔单抗组（第0/7/14/28/42/56/70/90天给予200mg，此后每月一次）加MMF或IR-TAC（每日0.1mg/kg；第0-30天目标C 4-11ng/mL，然后2-5ng/mL）。所有患者均接受巴利昔单抗诱导治疗（移植前及移植后第3-5天给予20mg）和糖皮质激素治疗。138名移植受者接受了≥1剂研究药物（SoC组[n = 48]；布莱昔单抗+MMF组[n = 46]；布莱昔单抗+IR-TAC组[n = 44]）。对于主要终点（6个月时活检证实的急性排斥反应[BPAR]发生率），布莱昔单抗+IR-TAC不劣于SoC组（差异2.8%；95%置信区间[CI]-8.1%至13.8%），而布莱昔单抗+MMF未显示不劣于SoC组（差异30.7%；95%CI 15.2%-46.2%）。在所有组中，BPAR发生率在36个月内略有上升，布莱昔单抗+IR-TAC组继续显示不劣于SoC组。布莱昔单抗具有良好的效益风险比。大多数治疗中出现的不良事件与肾移植受者预期的一致（ClinicalTrials.gov NCT01780844）。
