Belatacept as an alternative immunosuppressive agent for bone marrow-sparing in idiopathic pulmonary fibrosis lung transplant recipients with short telomeres

Stefanie J Hannan; Carlo J Iasella; Michel Sciullo; Cody Moore; Ryan Rivosecci; Lauren Sacha; Rachel M Sutton; Ritchie Koshy; Norihisa Shigemura; Pablo G Sanchez; Rafic Farah; Chadi A Hage; Jonathan K Alder; John F McDyer

doi:10.1016/j.healun.2025.04.022

Belatacept as an alternative immunosuppressive agent for bone marrow-sparing in idiopathic pulmonary fibrosis lung transplant recipients with short telomeres

J Heart Lung Transplant. 2025 May 7:S1053-2498(25)01961-8. doi: 10.1016/j.healun.2025.04.022. Online ahead of print.

Authors

Affiliations

¹ Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania; Lung Transplant Research Center, University of Pittsburgh, Pittsburgh, Pennsylvania.
² Department of Pharmacy and Therapeutics, University of Pittsburgh, Pittsburgh, Pennsylvania; Lung Transplant Research Center, University of Pittsburgh, Pittsburgh, Pennsylvania.
³ Department of Pharmacy and Therapeutics, University of Pittsburgh, Pittsburgh, Pennsylvania.
⁴ Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Cardiothoracic Surgery, University of Pittsburgh, Chicago, Illinois.
⁵ Department of Surgery, University of Chicago.
⁶ Medical Center, Hillman Cancer Center, University of Pittsburgh, Pittsburgh, Pennsylvania.
⁷ Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania; Lung Transplant Research Center, University of Pittsburgh, Pittsburgh, Pennsylvania. Electronic address: mcdyerjf@upmc.edu.

PMID: 40345564
DOI: 10.1016/j.healun.2025.04.022

Abstract

As we have previously shown, idiopathic pulmonary fibrosis lung transplant recipients (IPF-LTRs) with short-telomere length are prone to develop significant cytopenias and poor tolerance to cell-cycle inhibitors, specifically mycophenolate mofetil (MMF), post transplant. We investigated the use of belatacept as an alternative immunosuppressive agent in a prospective, open-label cohort of 9 ST-IPF-LTRs at our institution. These patients were either challenged with MMF (majority) or immediately started on belatacept post transplant with the goal to bridge to everolimus, an mammalian target of rapamycin inhibitor that is commonly used post transplant. We describe outcomes in the first-year post transplant, including the incidence of acute cellular rejection, Epstein-Barr virus viremia, and 1 case of post-transplant lymphoproliferative disorder (PTLD) at 13 months. The use of belatacept postlung transplant may be an acceptable short-term alternative therapy to cell-cycle inhibitors in ST-IPF-LTRs with cytopenias but may lead to a higher risk of Epstein-Barr Virus viremia and PTLD when belatacept is used long term in these patients.

Keywords: belatacept; lung transplantation; post-transplant lymphoproliferative disorder; pulmonary fibrosis; telomere.