蒽环类药物诱导的心肌病心力衰竭患者的同种异体间充质细胞治疗：CCTRN SENECA试验。
Allogeneic Mesenchymal Cell Therapy in Anthracycline-Induced Cardiomyopathy Heart Failure Patients: The CCTRN SENECA Trial.
作者信息
Bolli Roberto, Perin Emerson C, Willerson James T, Yang Phillip C, Traverse Jay H, Henry Timothy D, Pepine Carl J, Mitrani Raul D, Hare Joshua M, Murphy Michael P, March Keith L, Ikram Sohail, Lee David P, O'Brien Connor, Durand Jean-Bernard, Miller Kathy, Lima Joao A, Ostovaneh Mohammad R, Ambale-Venkatesh Bharath, Gee Adrian P, Richman Sara, Taylor Doris A, Sayre Shelly L, Bettencourt Judy, Vojvodic Rachel W, Cohen Michelle L, Simpson Lara M, Lai Dejian, Aguilar David, Loghin Catalin, Moyé Lem, Ebert Ray F, Davis Barry R, Simari Robert D
机构信息
Department of Medicine, Division of Cardiovascular Medicine, University of Louisville, School of Medicine, Louisville, Kentucky, USA.
Division of Cardiology Research, Texas Heart Institute, CHI St. Luke's Health Baylor College of Medicine Medical Center, Houston, Texas, USA.
出版信息
JACC CardioOncol. 2020 Nov;2(4):581-595. doi: 10.1016/j.jaccao.2020.09.001. Epub 2020 Dec 22.
BACKGROUND
Anthracycline-induced cardiomyopathy (AIC) may be irreversible with a poor prognosis, disproportionately affecting women and young adults. Administration of allogeneic bone marrow-derived mesenchymal stromal cells (allo-MSCs) is a promising approach to heart failure (HF) treatment.
OBJECTIVES
SENECA (Stem Cell Injection in Cancer Survivors) was a phase 1 study of allo-MSCs in AIC.
METHODS
Cancer survivors with chronic AIC (mean age 56.6 years; 68% women; NT-proBNP 1,426 pg/ml; 6 enrolled in an open-label, lead-in phase and 31 subjects randomized 1:1) received 1 × 10 allo-MSCs or vehicle transendocardially. Primary objectives were safety and feasibility. Secondary efficacy measures included cardiac function and structure measured by cardiac magnetic resonance imaging (CMR), functional capacity, quality of life (Minnesota Living with Heart Failure Questionnaire), and biomarkers.
RESULTS
A total of 97% of subjects underwent successful study product injections; all allo-MSC-assigned subjects received the target dose of cells. Follow-up visits were well-attended (92%) with successful collection of endpoints in 94% at the 1-year visit. Although 58% of subjects had non-CMR compatible devices, CMR endpoints were successfully collected in 84% of subjects imaged at 1 year. No new tumors were reported. There were no significant differences between allo-MSC and vehicle groups with regard to clinical outcomes. Secondary measures included 6-min walk test (p = 0.056) and Minnesota Living with Heart Failure Questionnaire score (p = 0.048), which tended to favor the allo-MSC group.
CONCLUSIONS
In this first-in-human study of cell therapy in patients with AIC, transendocardial administration of allo-MSCs appears safe and feasible, and CMR was successfully performed in the majority of the HF patients with devices. This study lays the groundwork for phase 2 trials aimed at assessing efficacy of cell therapy in patients with AIC.
背景
蒽环类药物诱导的心肌病（AIC）可能不可逆转，预后较差，对女性和年轻人的影响尤为严重。给予同种异体骨髓间充质基质细胞（allo-MSCs）是治疗心力衰竭（HF）的一种有前景的方法。
目的
SENECA（癌症幸存者干细胞注射）是一项关于allo-MSCs治疗AIC的1期研究。
方法
患有慢性AIC的癌症幸存者（平均年龄56.6岁；68%为女性；N末端脑钠肽前体1426 pg/ml；6人参加开放标签导入期，31名受试者按1:1随机分组）经心内膜接受1×10的allo-MSCs或赋形剂注射。主要目标是安全性和可行性。次要疗效指标包括通过心脏磁共振成像（CMR）测量的心脏功能和结构、功能能力、生活质量（明尼苏达心力衰竭生活问卷）和生物标志物。
结果
共有97%的受试者成功注射了研究产品；所有分配接受allo-MSCs的受试者均接受了目标剂量的细胞。随访就诊率良好（92%），1年随访时94%的受试者成功收集到终点数据。尽管58%的受试者有与CMR不兼容的装置，但1年时成像的受试者中84%成功收集到了CMR终点数据。未报告新的肿瘤。allo-MSCs组和赋形剂组在临床结局方面无显著差异。次要指标包括6分钟步行试验（p = 0.056）和明尼苏达心力衰竭生活问卷评分（p = 0.048），倾向于有利于allo-MSCs组。
结论
在这项针对AIC患者的细胞治疗的首次人体研究中，经心内膜给予allo-MSCs似乎是安全可行的，并且大多数有装置的HF患者成功进行了CMR检查。这项研究为评估细胞治疗对AIC患者疗效的2期试验奠定了基础。
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