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Randomized Controlled Trial
. 2024 Mar 1;108(3):777-786.
doi: 10.1097/TP.0000000000004841. Epub 2024 Feb 20.

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

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

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

Howard J Huang et al. 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.

Trial registration: ClinicalTrials.gov NCT03388008.

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Conflict of interest statement

M.A. is on the scientific advisory board of Immunocoer and One Lambda. V.P. is a consultant for PrecisCa. D.K. is on the scientific advisory board of Sana Biotechnology. R.H. received grant funding from Bristol Myers Squibb. The other authors declare no conflicts of interest.

Figures

Figure 1.
Figure 1.
Study consort diagram.
Figure 2.
Figure 2.
The development of donor-specific antibodies (DSA). There was no significant difference in freedom from the development of DSA between the 2 groups.
Figure 3.
Figure 3.
Acute cellular rejection (ACR) and lymphocytic bronchiolitis (LB). There was no significant difference in freedom from ACR or LB between the 2 groups.
Figure 4.
Figure 4.
A. Freedom from chronic lung allograft dysfunction (CLAD); there was no significant difference in freedom from CLAD between the 2 groups. B. Patient survival; there was a significantly worse survival in the Belatacept arm compared to the Control arm (log rank p = 0.008).
Figure 5.
Figure 5.
Analyses of levels of NK, CD4+ and CD8+ naïve and memory T cell populations from peripheral blood mononuclear cells of 13 participants. There was a nonzero increase in NK cell abundance in the Belatacept arm which was absent in the control arm, but there were no significant differences in the frequency of CD4+ and CD8+ T cell naïve, central memory (TCM), effector memory (TEM), and effector memory cells expressing CD45RA (TEMRA) between the 2 arms.
See this image and copyright information in PMC

References

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