Challenges of calcineurin inhibitor withdrawal following combined pancreas and kidney transplantation: Results of a prospective, randomized clinical trial

• Type of Material: Article
• Authors: Peter G Stock, UCSF, San Francisco; Roslyn B Mannon, UAB, Birmingham; Brian Armstrong, Rho Inc; Natasha Watson, National Institute Allergy and Infectious Diseases; David Ikle, Rho Inc; Mark A Robien, National Institute Allergy and Infectious Diseases; Yvonne Morrison, National Institute Allergy and Infectious Diseases; Jon Odorico, University of Wisconsin Madison; Jonathan Fridell, IU, Indianapolis; Aneesh Mehta, Emory University; Kenneth Newell, Emory University
• Language: English
• Date: 2020-06-01
• Publisher: WILEY
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2020 American Society of Transplantation & American Society of Transplant Surgeons. Published by Elsevier Inc. All rights reserved.
• Final Published Version (URL): http://dx.doi.org/10.1111/ajt.15817
• Title of Journal or Parent Work: AMERICAN JOURNAL OF TRANSPLANTATION
• Volume: 20
• Issue: 6
• Start Page: 1668
• End Page: 1678
• Keywords: tacrolimus; immunosuppressant-calcineurin inhibitor; practice; diabetes; DACLIZUMAB; simultaneous pancreas-kidney transplantation; type 1; LONG-TERM; Transplantation; Life Sciences & Biomedicine; Science & Technology; immune modulation; rejection; clinical research; immunosuppression; costimulation; acute; BELATACEPT-RESISTANT REJECTION; MYCOPHENOLATE-MOFETIL; sensitization; THERAPY; ONSET DIABETES-MELLITUS; MULTICENTER TRIAL; pancreas; RECIPIENTS; Surgery

Abstract

In a phase 2 multicenter open-label randomized trial sponsored by the National Institutes of Health, simultaneous pancreas-kidney (SPK) recipients were randomized to a calcineurin inhibitor (CNI)–based immunosuppressive regimen (tacrolimus) (n = 21), or an investigational arm using low-dose CNI plus costimulation blockade (belatacept) with intended CNI withdrawal (n = 22). Both arms included induction therapy with rabbit ATG, mycophenolate sodium, or mycophenolate mofetil and rapid withdrawal of steroids. Enrollment and CNI withdrawal were stopped after 43/60 planned subjects had been enrolled. At that time, the rate of biopsy-proven acute rejection (BPAR) of the pancreas was low in both groups until CNI was withdrawn, with four of the five pancreas rejections occurring during or after CNI withdrawal. The rate of BPAR of kidney allografts was low in both control (9.5%) and investigational (9.1%) arms. Pancreas graft survival at 52 weeks, defined by insulin independence, was 21 (100%) in the control group and 19 (86%) in the investigational arm. One subject in the investigational arm died with functioning pancreas and kidney grafts. Renal function at week 52 was similar in both arms. Costimulation blockade with belatacept did not provide sufficient immunosuppression to reliably prevent pancreas rejection in SPK transplants undergoing CNI withdrawal.