Leslie S Kean, Linda J Burns, Tzuyung D Kou, Roxanne Kapikian, Karissa Lozenski, Amelia Langston, John T Horan, Benjamin Watkins, Muna Qayed, Brandi Bratrude, Kayla Betz, Xiao-Ying Tang, Mei-Jie Zhang, Sean E Connolly, Martin Polinsky, Brian Gavin, Andres Gomez-Caminero, Marcelo C Pasquini
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Primary outcomes included day-180, 1-year, and 2-year overall survival (OS) and relapse-free survival (RFS) for abatacept + CNI/MTX vs CNI/MTX, CNI/MTX + antithymocyte globulin (ATG), and posttransplant cyclophosphamide-based prophylaxis (PT-Cy). For 7/8 MMUDs, day-180 OS (primary end point supporting FDA approval) was significantly higher for abatacept + CNI/MTX vs CNI/MTX (98% vs 75%; P = .0028). Two-year RFS was significantly higher for abatacept + CNI/MTX vs CNI/MTX (74% vs 49%; P = .0098) and CNI/MTX + ATG (77% vs 35%; P = .0002), and similar vs PT-Cy (72% vs 56%; P = .1058). For 8/8 MUDs, 2-year RFS for abatacept + CNI/MTX was numerically higher vs CNI/MTX (63% vs 52%; P = .1497), with an improved hazard ratio (HR) of 0.46 (0.25-0.86), and vs CNI/MTX + ATG (66% vs 55%; P = .1193; HR, 0.39 [0.21-0.73]), and was similar vs PT-Cy (68% vs 57%; P = .2356; HR, 0.54 [0.26-1.11]). 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引用次数: 0
摘要
阿帕他赛联合钙神经蛋白抑制剂/甲氨蝶呤（CNI/MTX）是美国食品及药物管理局（FDA）批准的首个在非亲缘供体造血细胞移植（URD-HCT）过程中预防急性移植物抗宿主病（aGVHD）的方案。我们利用国际血液和骨髓移植研究中心（Center for International Blood and Marrow Transplant Research）2011-2018年间7/8-人类白细胞抗原（HLA）不匹配（MMUD）或8/8-HLA匹配（MUD）URD-HCT受者的数据，研究了其对URD-HCT患者的影响。主要结果包括阿巴他赛普+CNI/MTX与CNI/MTX、CNI/MTX+抗胸腺细胞球蛋白（ATG）和移植后环磷酰胺预防疗法（PT-Cy）的180天、1年和2年总生存期（OS）和无复发生存期（RFS）；其他结果包括aGVHD、慢性GVHD、非复发死亡率和复发。对于7/8-MMUDs，阿巴他赛普+CNI/MTX与CNI/MTX相比，180天OS（支持FDA批准的主要终点）显著更高（98%vs75%；P=0.0028）。阿巴他赛普+CNI/MTX与CNI/MTX（83%vs55%；p=0.0036）、CNI/MTX+ATG（83%vs46%；p=0.0005）相比，两年OS明显更高，与PT-Cy相似（80%vs68%；p=0.2325）。阿巴他赛普+CNI/MTX与CNI/MTX（74%vs49%；p=0.0098）和CNI/MTX+ATG（77%vs35%；p=0.0002）相比，两年RFS明显更高，与PT-Cy相似（72%vs56%；p=0.1058）。对于8/8-MUDs，阿巴他赛普+CNI/MTX与CNI/MTX（70%vs62%；p=0.2569）、CNI/MTX+ATG（75%vs64%；p=0.1048）和PT-Cy（74%vs69%；p=0.5543）的2年OS相似。阿巴他赛普+CNI/MTX与CNI/MTX（63%vs52%；p=0.1497）和CNI/MTX+ATG（66%vs55%；p=0.1193；HR：0.39 [0.21-0.73]）相比，阿巴他赛普+CNI/MTX的两年RFS在数字上更高，危险比（HR：0.46 [0.25-0.86]）也更高。与 PT-Cy 相比，两年 RFS 相似（68%vs57%；P=0.2356；HR：0.54 [0.26-1.11]）。对于7/8-MMUD和8/8-MUD受者，阿巴他赛普+CNI/MTX预防与CNI/MTX和CNI/MTX+ATG相比可改善生存预后；与基于PT-Cy的方案相比，结果相似。阿巴他赛普+CNI/MTX有可能促进非亲属捐献者库的扩大，从而促进造血干细胞移植。
Abatacept for acute graft-versus-host disease prophylaxis after unrelated donor hematopoietic cell transplantation.
Abstract: Abatacept plus calcineurin inhibitors/methotrexate (CNI/MTX) is the first US Food and Drug Administration (FDA)-approved regimen for acute graft-versus-host disease (aGVHD) prophylaxis during unrelated-donor hematopoietic cell transplantation (URD-HCT). Using Center for International Blood and Marrow Transplant Research data, we investigated its impact in patients receiving 7/8 HLA-mismatched unrelated donor (MMUD) or 8/8 HLA-matched unrelated donor (MUD) URD-HCT between 2011 and 2018. Primary outcomes included day-180, 1-year, and 2-year overall survival (OS) and relapse-free survival (RFS) for abatacept + CNI/MTX vs CNI/MTX, CNI/MTX + antithymocyte globulin (ATG), and posttransplant cyclophosphamide-based prophylaxis (PT-Cy). For 7/8 MMUDs, day-180 OS (primary end point supporting FDA approval) was significantly higher for abatacept + CNI/MTX vs CNI/MTX (98% vs 75%; P = .0028). Two-year RFS was significantly higher for abatacept + CNI/MTX vs CNI/MTX (74% vs 49%; P = .0098) and CNI/MTX + ATG (77% vs 35%; P = .0002), and similar vs PT-Cy (72% vs 56%; P = .1058). For 8/8 MUDs, 2-year RFS for abatacept + CNI/MTX was numerically higher vs CNI/MTX (63% vs 52%; P = .1497), with an improved hazard ratio (HR) of 0.46 (0.25-0.86), and vs CNI/MTX + ATG (66% vs 55%; P = .1193; HR, 0.39 [0.21-0.73]), and was similar vs PT-Cy (68% vs 57%; P = .2356; HR, 0.54 [0.26-1.11]). For 7/8 MMUD and 8/8 MUD recipients, abatacept + CNI/MTX prophylaxis improved survival outcomes vs CNI/MTX and CNI/MTX + ATG; outcomes were similar to PT-Cy-based regimens. Abatacept + CNI/MTX may facilitate unrelated donor pool expansion for HCT.
期刊介绍：
Blood, the official journal of the American Society of Hematology, published online and in print, provides an international forum for the publication of original articles describing basic laboratory, translational, and clinical investigations in hematology. Primary research articles will be published under the following scientific categories: Clinical Trials and Observations; Gene Therapy; Hematopoiesis and Stem Cells; Immunobiology and Immunotherapy scope; Myeloid Neoplasia; Lymphoid Neoplasia; Phagocytes, Granulocytes and Myelopoiesis; Platelets and Thrombopoiesis; Red Cells, Iron and Erythropoiesis; Thrombosis and Hemostasis; Transfusion Medicine; Transplantation; and Vascular Biology. Papers can be listed under more than one category as appropriate.
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