Leung Nelson, Comenzo Raymond, Gillmore Julian, Havasi Andrea, Kastritis Efstathios, Guthrie Spencer, Signorovitch James, Heath Dena, Lousada Isabelle
Mayo Clinic, Rochester, Minnesota, USA.
Tufts Medical Center, Tufts University School of Medicine, Boston, Massachusetts, USA.
Kidney Int Rep. 2024 Apr 4;9(7):1986-1994. doi: 10.1016/j.ekir.2024.03.033. eCollection 2024 Jul.
Immunoglobin light chain (AL) amyloidosis is a rare disease characterized by organ deposition of amyloid fibrils, most commonly in the heart and kidney. Disease heterogeneity necessitates organ-specific assessment to determine prognosis and response or progression. To facilitate development of new therapies, the Amyloidosis Forum (a public-private partnership between the US Food and Drug Administration and the nonprofit Amyloidosis Research Consortium) held a series of meetings and formed multiple working groups to identify clinical trial end points and analytic strategies. This report summarizes the recommendations of Renal Working Group. Estimated glomerular filtration rate (eGFR) and proteinuria were selected to evaluate eligibility, response, and/or progression in the context of investigational clinical trials for patients with AL amyloidosis. Accurate response assessments at the earliest possible time point were emphasized. The context of use, specific patient population, and the investigational therapeutic mechanism should ultimately drive selection of appropriate end points to evaluate renal response/progression in AL amyloidosis clinical trials.
免疫球蛋白轻链(AL)淀粉样变性是一种罕见疾病,其特征为淀粉样原纤维在器官沉积,最常见于心脏和肾脏。疾病的异质性需要进行器官特异性评估以确定预后以及反应或进展情况。为推动新疗法的研发,淀粉样变性论坛(美国食品药品监督管理局与非营利性淀粉样变性研究联盟之间的公私合营机构)召开了一系列会议,并组建了多个工作组以确定临床试验终点和分析策略。本报告总结了肾脏工作组的建议。在针对AL淀粉样变性患者的研究性临床试验中,选择估计肾小球滤过率(eGFR)和蛋白尿来评估入选资格、反应和/或进展情况。强调应在尽可能早的时间点进行准确的反应评估。使用背景、特定患者群体以及研究性治疗机制最终应推动选择合适的终点来评估AL淀粉样变性临床试验中的肾脏反应/进展情况。