Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
Division of Pharmacology, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
Bone Marrow Transplant. 2021 Dec;56(12):3029-3031. doi: 10.1038/s41409-021-01460-1. Epub 2021 Sep 21.
Alemtuzumab is used as part of reduced-intensity and reduced-toxicity transplant conditioning regimens for nonmalignant diseases. Prior studies identified an ideal target concentration range of 0.15-0.6 mcg/mL at day 0. However, only 24% of patients fall within this window using standard intermediate dosing. We performed a pilot study of a novel target concentration intervention strategy to target day 0 alemtuzumab concentrations to 0.15-0.6 mcg/mL. Twelve patients received model-informed alemtuzumab dosing of 0.5-0.6 mcg/kg divided over days -14 to -12. Alemtuzumab concentrations were measured, and pharmacokinetic (PK) modeling was performed on day -5 to predict day 0 concentrations. If the day 0 alemtuzumab concentration was predicted to fall below 0.15 mcg/mL, simulations were performed to identify the individual "top-up" dose needed to achieve the target day 0 concentration window. Six (50%) patients achieved day 0 alemtuzumab concentrations between 0.15 and 0.6 mcg/mL (4 received a top-up dose). Five patients had day 0 concentrations above the target window (no top-up doses). One patient had a day 0 concentration below the target range in the presence of anti-alemtuzumab antibodies. A concentration intervention strategy approach to alemtuzumab treatment can successfully target a greater proportion of patients into the ideal therapeutic window. Additional dose-reduction studies are needed to further optimize the initial dosing and achieve target attainment in all patients.
阿仑单抗被用于非恶性疾病的低强度和降低毒性的移植预处理方案的一部分。先前的研究确定了 0 天的理想目标浓度范围为 0.15-0.6μg/ml。然而，只有 24%的患者在标准中等剂量范围内。我们进行了一项新的目标浓度干预策略的试点研究，以将 0 天阿仑单抗的浓度靶向 0.15-0.6μg/ml。12 名患者接受了 0.5-0.6μg/kg 的模型指导的阿仑单抗剂量治疗，在-14 天至-12 天内分服。测量阿仑单抗浓度，并在-5 天至 0 天进行药代动力学（PK）建模，以预测 0 天的浓度。如果预测 0 天的阿仑单抗浓度低于 0.15μg/ml，则进行模拟以确定达到目标 0 天浓度窗口所需的个体“补充”剂量。6 名（50%）患者达到了 0 天的阿仑单抗浓度在 0.15 和 0.6μg/ml 之间（4 名患者接受了补充剂量）。5 名患者的 0 天浓度超过了目标范围（无补充剂量）。1 名患者在存在抗阿仑单抗抗体的情况下，0 天浓度低于目标范围。阿仑单抗治疗的浓度干预策略方法可以成功地将更大比例的患者靶向到理想的治疗窗口。需要进一步的剂量减少研究来优化初始剂量，并使所有患者达到目标。
