Treatment of De Novo Renal Transplant Recipients With Calcineurin Inhibitor–free, Belatacept Plus Everolimus–based Immunosuppression

V. Ram Peddi, MD; Bradley Marder, MD; Luis Gaite, MD; Jose Oberholzer, MD; Ryan Goldberg, MD; Thomas Pearson, MD; Harold Yang, MD, PhD; Lisa Allamassey, MSc; Martin Polinsky, MD; Richard N. Formica, MD

doi:10.1097/TXD.0000000000001419

Transplantation Direct (Feb 2023)

Treatment of De Novo Renal Transplant Recipients With Calcineurin Inhibitor–free, Belatacept Plus Everolimus–based Immunosuppression

V. Ram Peddi, MD,
Bradley Marder, MD,
Luis Gaite, MD,
Jose Oberholzer, MD,
Ryan Goldberg, MD,
Thomas Pearson, MD,
Harold Yang, MD, PhD,
Lisa Allamassey, MSc,
Martin Polinsky, MD,
Richard N. Formica, MD

Affiliations

V. Ram Peddi, MD: 1 Department of Transplantation, California Pacific Medical Center, San Francisco, CA.
Bradley Marder, MD: 2 Division of Transplant Research, Colorado Kidney Care, Denver, CO.
Luis Gaite, MD: 3 Sección Hepatología, Clinica de Nefrología, Santa Fe, Argentina.
Jose Oberholzer, MD: 4 Division of Transplant Surgery, Department of Surgery, University of Virginia Health System, Charlottesville, VA.
Ryan Goldberg, MD: 5 Renal and Pancreas Transplant Division, Saint Barnabas Medical Center, Livingston, NJ.
Thomas Pearson, MD: 6 Emory Transplant Center, Department of Surgery, Emory University School of Medicine, Atlanta, GA.
Harold Yang, MD, PhD: 7 Department of Surgery, University of Pittsburgh Medical Center Pinnacle, Harrisburg, PA.
Lisa Allamassey, MSc: 8 Bristol Myers Squibb, Braine I’Alleud, Belgium.
Martin Polinsky, MD: 9 Bristol Myers Squibb, Princeton, NJ.
Richard N. Formica, MD: 10 Section of Nephrology, Yale School of Medicine, New Haven, CT.

DOI: https://doi.org/10.1097/TXD.0000000000001419
Journal volume & issue: Vol. 9, no. 2
p. e1419

Abstract

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Background. Compared with calcineurin inhibitor–based immunosuppression, belatacept (BELA)-based treatment has been associated with better renal function but higher acute rejection rates. This phase 2 study (NCT02137239) compared the antirejection efficacy of BELA plus everolimus (EVL) with tacrolimus (TAC) plus mycophenolate mofetil (MMF), each following lymphocyte-depleting induction and rapid corticosteroid withdrawal. Methods. Patients who were de novo renal transplant recipients seropositive for Epstein-Barr virus were randomized to receive BELA+EVL or TAC+MMF maintenance therapy after rabbit antithymocyte globulin induction and up to 7 d of corticosteroids. The primary endpoint was the rate of biopsy-proven acute rejection at month 6. Results. Because of an unanticipated BELA supply constraint, enrollment was prematurely terminated at 68 patients, of whom 58 were randomized and transplanted (intention-to-treat [ITT] population: n = 26, BELA+EVL; n = 32, TAC+MMF). However, 25 patients received BELA+EVL‚ and 33 received TAC+MMF (modified ITT population). In the ITT population, the 6-mo biopsy-proven acute rejection rates were 7.7% versus 9.4% in the BELA+EVL versus TAC+MMF group. The corresponding 24-mo biopsy-proven acute rejection rates were 19.2% versus 12.5% in the ITT population and 16.0% versus 15.2% in the mITT population; all events were Banff severity grade ≤IIA and similar between groups. One patient in each group experienced graft loss unrelated to acute rejection. The 24-mo mean unadjusted estimated glomerular filtration rates were 71.8 versus 68.7 mL/min/1.73 m2 in the BELA+EVL versus TAC+MMF groups. Posttransplant lymphoproliferative disorder was reported for 1 patient in each group. No deaths or unexpected adverse events were observed. Conclusions. A steroid-free maintenance regimen of BELA+EVL may be associated with biopsy-proven acute rejection rates comparable to TAC+MMF.

Published in Transplantation Direct

ISSN: 2373-8731 (Online)
Publisher: Wolters Kluwer
Country of publisher: United States
LCC subjects: Medicine: Surgery
Website: http://journals.lww.com/transplantationdirect/Pages/default.aspx

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