A prospective multi-institutional study of eculizumab to treat high-risk stem cell transplantation–associated TMA

伊库利珠单抗 医学 血栓性微血管病 内科学 临床终点 造血干细胞移植 肾功能 移植 前瞻性队列研究 胃肠病学 累积发病率 外科 免疫学 补体系统 临床试验 免疫系统 疾病
作者
Sonata Jodele,Christopher E. Dandoy,Paibel Aguayo‐Hiraldo,Adam Lane,Ashley Teusink‐Cross,Anthony Sabulski,Kana Mizuno,Benjamin L. Laskin,Jason L. Freedman,Stella M. Davies
出处
期刊:Blood [Elsevier BV]
卷期号:143 (12): 1112-1123 被引量:11
标识
DOI:10.1182/blood.2023022526
摘要

Abstract High-risk, complement mediated, untreated transplant-associated thrombotic microangiopathy (hrTMA) has dismal outcomes due to multi-organ dysfunction syndrome (MODS). The complement C5 blocker eculizumab shows promising results in hrTMA, but has not been prospectively studied in hematopoietic stem cell transplant (HCT) recipients. We performed the first multi-institutional prospective study in children and young adults to evaluate eculizumab as an early targeted intervention for hrTMA/MODS. We hypothesized that eculizumab would more than double survival in HCT recipients with hrTMA, compared to our prior study of prospectively screened, untreated hrTMAs serving as historical controls. HrTMA features (elevated terminal complement (sC5b-9) and proteinuria measured by random urine protein/creatinine ratio (≥1mg/mg)) were required for inclusion. The primary endpoint was survival at 6 six-months from hrTMA diagnosis. Secondary endpoints were cumulative incidence of MODS 6 months after hrTMA diagnosis and 1-year posttransplant survival. Eculizumab dosing included intensive loading, induction, and maintenance phases for up to 24 weeks of therapy. All 21 evaluated study subjects had MODS. Primary and secondary study endpoints were met by demonstrating survival of 71% (P < .0001) 6 months after hrTMA diagnosis and 62% 1 year after transplant. Of fifteen survivors, 11 (73%) fully recovered organ function and are well. Our study demonstrates significant improvement in survival and recovery of organ function in hrTMA using an intensified eculizumab dosing and real time biomarker monitoring. This study serves as a benchmark for planning future studies that should focus on preventative measures or targeted therapy to be initiated prior to organ injury. This trial was registered at www.clinicaltrials.gov as #NCT03518203.
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