A Phase 3, Single-Arm, Prospective Study of Remestemcel-L, Ex Vivo Culture-Expanded Adult Human Mesenchymal Stromal Cells for the Treatment of Pediatric Patients Who Failed to Respond to Steroid Treatment for Acute Graft-versus-Host Disease

被引：114

作者：

Kurtzberg, Joanne ^{[1
]}

Abdel-Azim, Hisham ^{[2
]}

Carpenter, Paul ^{[3
]}

Chaudhury, Sonali ^{[4
]}

Horn, Biljana ^{[5
]}

Mahadeo, Kris ^{[6
]}

Nemecek, Eneida ^{[7
]}

Neudorf, Steven ^{[8
]}

Prasad, Vinod ^{[1
]}

Prockop, Susan ^{[9
]}

Quigg, Troy ^{[10
]}

Satwani, Prakash ^{[11
]}

Cheng, Annie ^{[12
]}

Burke, Elizabeth ^{[12
]}

Hayes, Jack ^{[12
]}

Skerrett, Donna ^{[12
]}

机构：

[1] Duke Univ, Med Ctr, Durham, NC 27705 USA

[2] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA

[3] Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA

[4] Ann & Robert H Lurie Childrens Hosp Chicago, Chicago, IL 60611 USA

[5] UCSF Benioff Childrens Hosp, San Francisco, CA USA

[6] Albert Einstein Coll Med, New York, NY USA

[7] Oregon Hlth & Sci Univ, Portland, OR 97201 USA

[8] Childrens Hosp Orange Cty, Orange, CA 92668 USA

[9] MSK Kids, New York, NY USA

[10] Texas Transplant Inst, San Antonio, TX USA

[11] Columbia Univ, Med Ctr, New York, NY USA

[12] Mesoblast Inc, New York, NY USA

来源：

BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION | 2020年 / 26卷 / 05期

关键词：

Acute graft-versus-host disease; Allogeneic; Hematopoietic stem cell transplantation; Mesenchymal stromal cells; Remestemcel-L; Steroid; RESISTANT ACUTE GVHD; STEM-CELLS; SURVIVAL; THERAPY; IMMUNOMODULATION; PROLIFERATION; SEVERITY;

D O I：

10.1016/j.bbmt.2020.01.018

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Steroid-refractory acute graft-versus-host disease (SR-aGVHD) following hematopoietic cell transplantation (HSCT) is associated with poor clinical outcomes. Currently, there are no safe and effective therapies approved for use in the pediatric population under the age of 12 years. Accordingly, there is an urgent need for new treatments that are safe, well tolerated, and effective in managing this debilitating and potentially fatal complication of HSCT. In early phase clinical trials, mesenchymal stromal cells (MSCs) have demonstrated efficacy in the treatment of acute GVHD (aGVHD) in pediatric patients. We now report the results of a phase 3, prospective, single-arm, multicenter study (NCT02336230) in 54 children with primary SR-aGVHD who were naive to other immunosuppressant therapies for aGVHD treated with MSC product (remestemcel-L) dosed at 2 x 10(6) cells/kg twice weekly for 4 weeks. Remestemcel-L therapy significantly improved day 28 overall response rate (OR) compared with the prespecified control OR value of 45% (70.4% versus 45%, P = .0003). The statistically significant OR (70.4%) was sustained through day 100, including an increase in complete response from 29.6% at day 28 to 44.4% at day 100. Overall survival was 74.1% at day 100 and 68.5% at day 180. Overall response in all participants at day 28 was highly predictive of improved survival through 180 days, and survival was significantly greater in day 28 responders compared with nonresponders through day 100 (86.8% versus 47.1% for responders and nonresponders, respectively, P = .0001) and through day 180 (78.9% versus 43.8%, P = .003). Remestemcel-L was well tolerated with no identified infusion-related toxicities or other safety concerns. This study provides robust, prospective evidence of the safety, tolerability, and efficacy of remestemcel-L as first-line therapy after initial steroid failure in pediatric SR-aGVHD. (C) 2020 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.

引用

页码：845 / 854

页数：10

共 40 条

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