Prospective, Randomized, Double-Blind, Phase III Clinical Trial of Anti–T-Lymphocyte Globulin to Assess Impact on Chronic Graft-Versus-Host Disease–Free Survival in Patients Undergoing HLA-Matched Unrelated Myeloablative Hematopoietic Cell Transplantation

Author:

Soiffer Robert J.1,Kim Haesook T.1,McGuirk Joseph1,Horwitz Mitchell E.1,Johnston Laura1,Patnaik Mrinal M.1,Rybka Witold1,Artz Andrew1,Porter David L.1,Shea Thomas C.1,Boyer Michael W.1,Maziarz Richard T.1,Shaughnessy Paul J.1,Gergis Usama1,Safah Hana1,Reshef Ran1,DiPersio John F.1,Stiff Patrick J.1,Vusirikala Madhuri1,Szer Jeff1,Holter Jennifer1,Levine James D.1,Martin Paul J.1,Pidala Joseph A.1,Lewis Ian D.1,Ho Vincent T.1,Alyea Edwin P.1,Ritz Jerome1,Glavin Frank1,Westervelt Peter1,Jagasia Madan H.1,Chen Yi-Bin1

Affiliation:

1. Robert J. Soiffer, Haesook T. Kim, Vincent T. Ho, Edwin P. Alyea, and Jerome Ritz, Dana-Farber Cancer Institute; James D. Levine, Beth Israel Deaconess Medical Center and Harvard Medical School; Yi-Bin Chen, Massachusetts General Hospital, Boston; Frank Glavin, Neovii Biotech, Lexington, MA; Joseph McGuirk, University of Kansas Medical Center, Kansas City, KS; Mitchell E. Horwitz, Duke University Medical Center, Durham; Thomas C. Shea, University of North Carolina School of Medicine, Chapel Hill, NC;...

Abstract

Purpose Several open-label randomized studies have suggested that in vivo T-cell depletion with anti–T-lymphocyte globulin (ATLG; formerly antithymocyte globulin-Fresenius) reduces chronic graft-versus-host disease (cGVHD) without compromising survival. We report a prospective, double-blind phase III trial to investigate the effect of ATLG (Neovii Biotech, Lexington, MA) on cGVHD-free survival. Patients and Methods Two hundred fifty-four patients 18 to 65 years of age with acute leukemia or myelodysplastic syndrome who underwent myeloablative HLA-matched unrelated hematopoietic cell transplantation (HCT) were randomly assigned one to one to placebo (n =128 placebo) or ATLG (n = 126) treatment at 27 sites. Patients received either ATLG or placebo 20 mg/kg per day on days −3, −2, −1 in addition to tacrolimus and methotrexate as GVHD prophylaxis. The primary study end point was moderate-severe cGVHD-free survival. Results Despite a reduction in grade 2 to 4 acute GVHD (23% v 40%; P = .004) and moderate-severe cGVHD (12% v 33%; P < .001) in ATLG recipients, no difference in moderate-severe cGVHD-free survival between ATLG and placebo was found (2-year estimate: 48% v 44%, respectively; P = .47). Both progression-free survival (PFS) and overall survival (OS) were lower with ATLG (2-year estimate: 47% v 65% [ P = .04] and 59% v 74% [ P = .034], respectively). Multivariable analysis confirmed that ATLG was associated with inferior PFS (hazard ratio, 1.55; 95% CI, 1.05 to 2.28; P = .026) and OS (hazard ratio, 1.74; 95% CI, 1.12 to 2.71; P = .01). Conclusion In this prospective, randomized, double-blind trial of ATLG in unrelated myeloablative HCT, the incorporation of ATLG did not improve moderate-severe cGVHD-free survival. Moderate-severe cGVHD was significantly lower with ATLG, but PFS and OS also were lower. Additional analyses are needed to understand the appropriate role for ATLG in HCT.

Publisher

American Society of Clinical Oncology (ASCO)

Subject

Cancer Research,Oncology

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3