costimulation blockade
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Author(s):  
Katsuyoshi Shimozawa ◽  
Laura Contreras‐Ruiz ◽  
Sofia Sousa ◽  
Ruan Zhang ◽  
Urvashi Bhatia ◽  
...  

Author(s):  
Christoph Schwarz ◽  
Benedikt Mahr ◽  
Moritz Muckenhuber ◽  
Anna Marianne Weijler ◽  
Lukas Walter Unger ◽  
...  

2021 ◽  
pp. JCO.20.01086
Author(s):  
Benjamin Watkins ◽  
Muna Qayed ◽  
Courtney McCracken ◽  
Brandi Bratrude ◽  
Kayla Betz ◽  
...  

PURPOSE Severe (grade 3-4) acute graft-versus-host disease (AGVHD) is a major cause of death after unrelated-donor (URD) hematopoietic cell transplant (HCT), resulting in particularly high mortality after HLA-mismatched transplantation. There are no approved agents for AGVHD prevention, underscoring the critical unmet need for novel therapeutics. ABA2 was a phase II trial to rigorously assess safety, efficacy, and immunologic effects of adding T-cell costimulation blockade with abatacept to calcineurin inhibitor (CNI)/methotrexate (MTX)-based GVHD prophylaxis, to test whether abatacept could decrease AGVHD. METHODS ABA2 enrolled adults and children with hematologic malignancies under two strata: a randomized, double-blind, placebo-controlled stratum (8/8-HLA-matched URD), comparing CNI/MTX plus abatacept with CNI/MTX plus placebo, and a single-arm stratum (7/8-HLA-mismatched URD) comparing CNI/MTX plus abatacept versus CNI/MTX CIBMTR controls. The primary end point was day +100 grade 3-4 AGVHD, with day +180 severe-AGVHD-free-survival (SGFS) a key secondary end point. Sample sizes were calculated using a higher type-1 error (0.2) as recommended for phase II trials, and were based on predicting that abatacept would reduce grade 3-4 AGVHD from 20% to 10% (8/8s) and 30% to 10% (7/8s). ABA2 enrolled 142 recipients (8/8s, median follow-up = 716 days) and 43 recipients (7/8s, median follow-up = 708 days). RESULTS In 8/8s, grade 3-4 AGVHD was 6.8% (abatacept) versus 14.8% (placebo) ( P = .13, hazard ratio = 0.45). SGFS was 93.2% (CNI/MTX plus abatacept) versus 82% (CNI/MTX plus placebo, P = .05). In the smaller 7/8 cohort, grade 3-4 AGVHD was 2.3% (CNI/MTX plus abatacept, intention-to-treat population), which compared favorably with a nonrandomized matched cohort of CNI/MTX (30.2%, P < .001), and the SGFS was better (97.7% v 58.7%, P < .001). Immunologic analysis revealed control of T-cell activation in abatacept-treated patients. CONCLUSION Adding abatacept to URD HCT was safe, reduced AGVHD, and improved SGFS. These results suggest that abatacept may substantially improve AGVHD-related transplant outcomes, with a particularly beneficial impact on HLA-mismatched HCT.


2020 ◽  
Author(s):  
Thomas Mühlbacher ◽  
Kerstin Amann ◽  
Moritz Mahling ◽  
Silvio Nadalin ◽  
Nils Heyne ◽  
...  

Abstract Recurrence of primary focal segmental glomerulosclerosis (FSGS) occurs in up to 50% of patients after kidney transplantation and is associated with poor allograft outcome. Novel therapeutic concepts directly target podocyte function via B7-1 with inconsistent response. We present the case of a 19 yr. old patient with recurrent primary FSGS early after living donor kidney transplantation. Plasmapheresis and rituximab did not induce remission. Repetitive abatacept administration was able to achieve partial remission. Maintenance immunosuppression was subsequently switched to a belatacept-based CNI-free immunosuppression, resulting in sustained complete remission with excellent allograft function throughout a follow-up of more than 56 months.


Author(s):  
Natalie M Edner ◽  
Chun Jing Wang ◽  
Lina Petersone ◽  
Lucy S K Walker

Abstract Curbing unwanted T cell responses by costimulation blockade has been a recognised immunosuppressive strategy for the last 15 years. However, our understanding of how best to deploy this intervention is still evolving. A key challenge has been the heterogeneity in the clinical response to costimulation blockade, and an inability to predict which individuals are likely to benefit most. Here we discuss our recent findings based on the use of costimulation blockade in people with type 1 diabetes (T1D) and place them in the context of the current literature. We discuss how profiling follicular helper T cells (Tfh) in pre-treatment blood samples may have value in predicting which individuals are likely to benefit from costimulation blockade drugs such as abatacept.


2020 ◽  
Vol 127 (8) ◽  
pp. 1115-1117 ◽  
Author(s):  
Elisa Martini ◽  
Marco Cremonesi ◽  
Cristina Panico ◽  
Pierluigi Carullo ◽  
Cecilia Assunta Bonfiglio ◽  
...  

2020 ◽  
Vol 11 ◽  
Author(s):  
Dimitrios Giannis ◽  
Dimitrios Moris ◽  
Linda C. Cendales

2020 ◽  
Vol 21 (10) ◽  
pp. 1244-1255 ◽  
Author(s):  
Natalie M. Edner ◽  
Frank Heuts ◽  
Niclas Thomas ◽  
Chun Jing Wang ◽  
Lina Petersone ◽  
...  

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