TY - JOUR
T1 - A pilot randomized controlled trial of de novo belatacept-based immunosuppression following anti-thymocyte globulin induction in lung transplantation
AU - Huang, Howard J.
AU - Schechtman, Kenneth
AU - Askar, Medhat
AU - Bernadt, Cory
AU - Mittler, Brigitte
AU - Dore, Peter
AU - Witt, Chad
AU - Byers, Derek
AU - Vazquez-Guillamet, Rodrigo
AU - Halverson, Laura
AU - Nava, Ruben
AU - Puri, Varun
AU - Gelman, Andrew
AU - Kreisel, Daniel
AU - Hachem, Ramsey R.
N1 - Publisher Copyright:
© 2022 The American Society of Transplantation and the American Society of Transplant Surgeons.
PY - 2022/7
Y1 - 2022/7
N2 - The development of donor-specific antibodies (DSA) after lung transplantation is common and results in adverse outcomes. In kidney transplantation, Belatacept has been associated with a lower incidence of DSA, but experience with Belatacept in lung transplantation is limited. We conducted a two-center pilot randomized controlled trial of de novo immunosuppression with Belatacept after lung transplantation to assess the feasibility of conducting a pivotal trial. Twenty-seven participants were randomized to Control (Tacrolimus, Mycophenolate Mofetil, and prednisone, n = 14) or Belatacept-based immunosuppression (Tacrolimus, Belatacept, and prednisone until day 89 followed by Belatacept, Mycophenolate Mofetil, and prednisone, n = 13). All participants were treated with rabbit anti-thymocyte globulin for induction immunosuppression. We permanently stopped randomization and treatment with Belatacept after three participants in the Belatacept arm died compared to none in the Control arm. Subsequently, two additional participants in the Belatacept arm died for a total of five deaths compared to none in the Control arm (log rank p =.016). We did not detect a significant difference in DSA development, acute cellular rejection, or infection between the two groups. We conclude that the investigational regimen used in this study is associated with increased mortality after lung transplantation. (Figure presented.).
AB - The development of donor-specific antibodies (DSA) after lung transplantation is common and results in adverse outcomes. In kidney transplantation, Belatacept has been associated with a lower incidence of DSA, but experience with Belatacept in lung transplantation is limited. We conducted a two-center pilot randomized controlled trial of de novo immunosuppression with Belatacept after lung transplantation to assess the feasibility of conducting a pivotal trial. Twenty-seven participants were randomized to Control (Tacrolimus, Mycophenolate Mofetil, and prednisone, n = 14) or Belatacept-based immunosuppression (Tacrolimus, Belatacept, and prednisone until day 89 followed by Belatacept, Mycophenolate Mofetil, and prednisone, n = 13). All participants were treated with rabbit anti-thymocyte globulin for induction immunosuppression. We permanently stopped randomization and treatment with Belatacept after three participants in the Belatacept arm died compared to none in the Control arm. Subsequently, two additional participants in the Belatacept arm died for a total of five deaths compared to none in the Control arm (log rank p =.016). We did not detect a significant difference in DSA development, acute cellular rejection, or infection between the two groups. We conclude that the investigational regimen used in this study is associated with increased mortality after lung transplantation. (Figure presented.).
KW - alloantibody
KW - clinical research/practice
KW - clinical trial
KW - immunosuppressant - fusion proteins and monoclonal antibodies: belatacept
KW - immunosuppression/immune modulation
KW - lung transplantation/pulmonology
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U2 - 10.1111/ajt.17028
DO - 10.1111/ajt.17028
M3 - Article
C2 - 35286760
AN - SCOPUS:85126743023
SN - 1600-6135
VL - 22
SP - 1884
EP - 1892
JO - American Journal of Transplantation
JF - American Journal of Transplantation
IS - 7
ER -