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Randomized Controlled Trial
. 2022 Jul;22(7):1884-1892.
doi: 10.1111/ajt.17028. Epub 2022 Mar 22.

A pilot randomized controlled trial of de novo belatacept-based immunosuppression following anti-thymocyte globulin induction in lung transplantation

Howard J Huang  1 , Kenneth Schechtman  2 , Medhat Askar  3 , Cory Bernadt  4 , Brigitte Mittler  5 , Peter Dore  2 , Chad Witt  5 , Derek Byers  5 , Rodrigo Vazquez-Guillamet  5 , Laura Halverson  5 , Ruben Nava  6 , Varun Puri  6 , Andrew Gelman  6 , Daniel Kreisel  6 , Ramsey R Hachem  5
Affiliations
Randomized Controlled Trial

A pilot randomized controlled trial of de novo belatacept-based immunosuppression following anti-thymocyte globulin induction in lung transplantation

Howard J Huang et al. Am J Transplant. 2022 Jul.

Abstract

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.

Keywords: alloantibody; clinical research/practice; clinical trial; immunosuppressant - fusion proteins and monoclonal antibodies: belatacept; immunosuppression/immune modulation; lung transplantation/pulmonology.

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Figures

Figure 1.
Figure 1.
Study consort diagram.
Figure 2.
Figure 2.
Patient survival. There was a significant survival difference between the Control group and the Belatacept group (log rank p = 0.016).
Figure 3.
Figure 3.
The development of donor-specific antibodies (DSA) to mismatched human leukocyte antigens (HLA). There was no significant difference in freedom from the development of DSA between the 2 groups.
Figure 4.
Figure 4.
Acute cellular rejection and lymphocytic bronchiolitis. There was no significant difference in freedom from acute cellular rejection (ACR) or lymphocytic bronchiolitis (LB) between the 2 groups.
See this image and copyright information in PMC

Comment in

  • Great expectations.
    Newell KA, Larsen CP. Newell KA, et al. Am J Transplant. 2022 Jul;22(7):1735-1736. doi: 10.1111/ajt.17048. Epub 2022 May 11. Am J Transplant. 2022. PMID: 35543181 No abstract available.

References

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