A Pilot Randomized Controlled Trial of De Novo Belatacept-based Immunosuppression After Lung Transplantation

Howard J Huang; Kenneth Schechtman; Medhat Askar; Cory Bernadt; Brigitte Mitter; Peter Dore; Ahmad Goodarzi; Simon Yau; J Georges Youssef; Chad A Witt; Derek E Byers; Rodrigo Vazquez-Guillamet; Laura Halverson; Ruben Nava; Varun Puri; Daniel Kreisel; Andrew E Gelman; Ramsey R Hachem

doi:10.1097/TP.0000000000004841

A Pilot Randomized Controlled Trial of De Novo Belatacept-based Immunosuppression After Lung Transplantation

Howard J Huang, Kenneth Schechtman, Medhat Askar, Cory Bernadt, Brigitte Mitter, Peter Dore, Ahmad Goodarzi, Simon Yau, J Georges Youssef, Chad A Witt, Derek E Byers, Rodrigo Vazquez-Guillamet, Laura Halverson, Ruben Nava, Varun Puri, Daniel Kreisel, Andrew E Gelman, Ramsey R Hachem

Research output: Contribution to journal › Article › peer-review

Abstract

BACKGROUND: Chronic lung allograft dysfunction (CLAD) is the leading cause of death beyond the first year after lung transplantation. The development of donor-specific antibodies (DSA) is a recognized risk factor for CLAD. Based on experience in kidney transplantation, we hypothesized that belatacept, a selective T-cell costimulatory blocker, would reduce the incidence of DSA after lung transplantation, which may ameliorate the risk of CLAD.

METHODS: We conducted a pilot randomized controlled trial (RCT) at 2 sites to assess the feasibility and inform the design of a large-scale RCT. All participants were treated with rabbit antithymocyte globulin for induction immunosuppression. Participants in the control arm were treated with tacrolimus, mycophenolate mofetil, and prednisone, and participants in the belatacept arm were treated with tacrolimus, belatacept, and prednisone through day 89 after transplant then converted to belatacept, mycophenolate mofetil, and prednisone for the remainder of year 1.

RESULTS: After randomizing 27 participants, 3 in the belatacept arm died compared with none in the control arm. As a result, we stopped enrollment and treatment with belatacept, and all participants were treated with standard-of-care immunosuppression. Overall, 6 participants in the belatacept arm died compared with none in the control arm (log rank P = 0.008). We did not observe any differences in the incidence of DSA, acute cellular rejection, antibody-mediated rejection, CLAD, or infections between the 2 groups.

CONCLUSIONS: We conclude that the investigational regimen used in this pilot RCT is associated with increased mortality after lung transplantation.

Original language	English (US)
Journal	Transplantation
DOIs	https://doi.org/10.1097/TP.0000000000004841
State	E-pub ahead of print - Oct 30 2023

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Huang, H. J., Schechtman, K., Askar, M., Bernadt, C., Mitter, B., Dore, P., Goodarzi, A., Yau, S., Youssef, J. G., Witt, C. A., Byers, D. E., Vazquez-Guillamet, R., Halverson, L., Nava, R., Puri, V., Kreisel, D., Gelman, A. E., & Hachem, R. R. (2023). A Pilot Randomized Controlled Trial of De Novo Belatacept-based Immunosuppression After Lung Transplantation. Transplantation. Advance online publication. https://doi.org/10.1097/TP.0000000000004841

Huang, HJ, Schechtman, K, Askar, M, Bernadt, C, Mitter, B, Dore, P, Goodarzi, A , Yau, S , Youssef, JG, Witt, CA, Byers, DE, Vazquez-Guillamet, R, Halverson, L, Nava, R, Puri, V, Kreisel, D, Gelman, AE & Hachem, RR 2023, 'A Pilot Randomized Controlled Trial of De Novo Belatacept-based Immunosuppression After Lung Transplantation', Transplantation. https://doi.org/10.1097/TP.0000000000004841

@article{26ebe20ae9a84960aa7ad8d4f86b5f33,

title = "A Pilot Randomized Controlled Trial of De Novo Belatacept-based Immunosuppression After Lung Transplantation",

abstract = "BACKGROUND: Chronic lung allograft dysfunction (CLAD) is the leading cause of death beyond the first year after lung transplantation. The development of donor-specific antibodies (DSA) is a recognized risk factor for CLAD. Based on experience in kidney transplantation, we hypothesized that belatacept, a selective T-cell costimulatory blocker, would reduce the incidence of DSA after lung transplantation, which may ameliorate the risk of CLAD.METHODS: We conducted a pilot randomized controlled trial (RCT) at 2 sites to assess the feasibility and inform the design of a large-scale RCT. All participants were treated with rabbit antithymocyte globulin for induction immunosuppression. Participants in the control arm were treated with tacrolimus, mycophenolate mofetil, and prednisone, and participants in the belatacept arm were treated with tacrolimus, belatacept, and prednisone through day 89 after transplant then converted to belatacept, mycophenolate mofetil, and prednisone for the remainder of year 1.RESULTS: After randomizing 27 participants, 3 in the belatacept arm died compared with none in the control arm. As a result, we stopped enrollment and treatment with belatacept, and all participants were treated with standard-of-care immunosuppression. Overall, 6 participants in the belatacept arm died compared with none in the control arm (log rank P = 0.008). We did not observe any differences in the incidence of DSA, acute cellular rejection, antibody-mediated rejection, CLAD, or infections between the 2 groups.CONCLUSIONS: We conclude that the investigational regimen used in this pilot RCT is associated with increased mortality after lung transplantation.",

author = "Huang, {Howard J} and Kenneth Schechtman and Medhat Askar and Cory Bernadt and Brigitte Mitter and Peter Dore and Ahmad Goodarzi and Simon Yau and Youssef, {J Georges} and Witt, {Chad A} and Byers, {Derek E} and Rodrigo Vazquez-Guillamet and Laura Halverson and Ruben Nava and Varun Puri and Daniel Kreisel and Gelman, {Andrew E} and Hachem, {Ramsey R}",

year = "2023",

month = oct,

day = "30",

doi = "10.1097/TP.0000000000004841",

language = "English (US)",

journal = "Transplantation",

issn = "0041-1337",

publisher = "Lippincott Williams and Wilkins",

}

TY - JOUR

T1 - A Pilot Randomized Controlled Trial of De Novo Belatacept-based Immunosuppression After Lung Transplantation

AU - Huang, Howard J

AU - Schechtman, Kenneth

AU - Askar, Medhat

AU - Bernadt, Cory

AU - Mitter, Brigitte

AU - Dore, Peter

AU - Goodarzi, Ahmad

AU - Yau, Simon

AU - Youssef, J Georges

AU - Witt, Chad A

AU - Byers, Derek E

AU - Vazquez-Guillamet, Rodrigo

AU - Halverson, Laura

AU - Nava, Ruben

AU - Puri, Varun

AU - Kreisel, Daniel

AU - Gelman, Andrew E

AU - Hachem, Ramsey R

PY - 2023/10/30

Y1 - 2023/10/30

N2 - BACKGROUND: Chronic lung allograft dysfunction (CLAD) is the leading cause of death beyond the first year after lung transplantation. The development of donor-specific antibodies (DSA) is a recognized risk factor for CLAD. Based on experience in kidney transplantation, we hypothesized that belatacept, a selective T-cell costimulatory blocker, would reduce the incidence of DSA after lung transplantation, which may ameliorate the risk of CLAD.METHODS: We conducted a pilot randomized controlled trial (RCT) at 2 sites to assess the feasibility and inform the design of a large-scale RCT. All participants were treated with rabbit antithymocyte globulin for induction immunosuppression. Participants in the control arm were treated with tacrolimus, mycophenolate mofetil, and prednisone, and participants in the belatacept arm were treated with tacrolimus, belatacept, and prednisone through day 89 after transplant then converted to belatacept, mycophenolate mofetil, and prednisone for the remainder of year 1.RESULTS: After randomizing 27 participants, 3 in the belatacept arm died compared with none in the control arm. As a result, we stopped enrollment and treatment with belatacept, and all participants were treated with standard-of-care immunosuppression. Overall, 6 participants in the belatacept arm died compared with none in the control arm (log rank P = 0.008). We did not observe any differences in the incidence of DSA, acute cellular rejection, antibody-mediated rejection, CLAD, or infections between the 2 groups.CONCLUSIONS: We conclude that the investigational regimen used in this pilot RCT is associated with increased mortality after lung transplantation.

AB - BACKGROUND: Chronic lung allograft dysfunction (CLAD) is the leading cause of death beyond the first year after lung transplantation. The development of donor-specific antibodies (DSA) is a recognized risk factor for CLAD. Based on experience in kidney transplantation, we hypothesized that belatacept, a selective T-cell costimulatory blocker, would reduce the incidence of DSA after lung transplantation, which may ameliorate the risk of CLAD.METHODS: We conducted a pilot randomized controlled trial (RCT) at 2 sites to assess the feasibility and inform the design of a large-scale RCT. All participants were treated with rabbit antithymocyte globulin for induction immunosuppression. Participants in the control arm were treated with tacrolimus, mycophenolate mofetil, and prednisone, and participants in the belatacept arm were treated with tacrolimus, belatacept, and prednisone through day 89 after transplant then converted to belatacept, mycophenolate mofetil, and prednisone for the remainder of year 1.RESULTS: After randomizing 27 participants, 3 in the belatacept arm died compared with none in the control arm. As a result, we stopped enrollment and treatment with belatacept, and all participants were treated with standard-of-care immunosuppression. Overall, 6 participants in the belatacept arm died compared with none in the control arm (log rank P = 0.008). We did not observe any differences in the incidence of DSA, acute cellular rejection, antibody-mediated rejection, CLAD, or infections between the 2 groups.CONCLUSIONS: We conclude that the investigational regimen used in this pilot RCT is associated with increased mortality after lung transplantation.

U2 - 10.1097/TP.0000000000004841

DO - 10.1097/TP.0000000000004841

M3 - Article

C2 - 37899481

SN - 0041-1337

JO - Transplantation

JF - Transplantation

ER -

A Pilot Randomized Controlled Trial of De Novo Belatacept-based Immunosuppression After Lung Transplantation

Abstract

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