Immune Checkpoint Inhibitors in Organ Transplant Patients

Adam S. Kittai, Hayden Oldham, Jeremy Cetnar, Matthew Taylor

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Modulation of T-cell activity through blockade of coinhibitory molecules has revolutionized the treatment of various malignancies. Several immune checkpoint inhibitors are currently Food and Drug Administration approved which target various coinhibitory pathways including cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed death 1 receptor (PD-1), and programmed cell death ligand-1. Clinical trials that lead to the Food and Drug Administration approval of these agents often excluded patients with an organ transplant. Excluding these patients was deliberate due to concern that immune checkpoint inhibitor therapy could lead to graft rejection. The PD-1 and CTLA-4 pathways are essential to downregulate our immune system in the setting of T-cell activation to prevent autoimmunity. Furthermore, both pathways are implicated in transplanted organ tolerance and modulation of the pathways may inadvertently lead to peripheral transplant rejection. Currently, there are no guidelines for the treatment of patients with immune checkpoint inhibitors in the setting of a prior organ transplant. Thus far, there are only 10 reported cases of patients in the literature who were treated in this setting. Two additional cases are reported herein, including 1 patient with a prior cardiac transplant receiving nivolumab for non–small cell lung cancer. Of the 12 cases, 4 patients experienced organ rejection. From these observations, the authors hypothesize factors that affect safety and of this treatment modality in this patient population. These factors include the integral role of the PD-1 pathway compared with the CTLA-4 pathway in organ acceptance, sequential implementation of different immune checkpoint inhibitor classes, length of time with a transplant before therapy, strength of immunosuppressive agents to prevent organ transplant rejection, and immunogenicity of the particular organ grafted. Although limited cases have been reported, there are circumstances in which immune checkpoint inhibitors have been used in the setting of organ transplantation without resulting in organ rejection. A thorough discussion with the patient of the potential risks, including graft rejection, and benefits of this therapy is necessary before beginning this treatment. More research is needed to explore the safety and efficacy of immune checkpoint inhibitors in the setting of organ transplantation.

Original languageEnglish (US)
JournalJournal of Immunotherapy
DOIs
StateAccepted/In press - Jul 17 2017

Fingerprint

Transplants
Graft Rejection
Death Domain Receptors
Cytotoxic T-Lymphocytes
Organ Transplantation
United States Food and Drug Administration
CD274 Antigen
Therapeutics
T-Lymphocytes
Drug Approval
Safety
Granzymes
Immunosuppressive Agents
Autoimmunity
Non-Small Cell Lung Carcinoma
Immune System
Proteins
Down-Regulation
Clinical Trials
Guidelines

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology
  • Cancer Research

Cite this

Immune Checkpoint Inhibitors in Organ Transplant Patients. / Kittai, Adam S.; Oldham, Hayden; Cetnar, Jeremy; Taylor, Matthew.

In: Journal of Immunotherapy, 17.07.2017.

Research output: Contribution to journalArticle

Kittai, Adam S. ; Oldham, Hayden ; Cetnar, Jeremy ; Taylor, Matthew. / Immune Checkpoint Inhibitors in Organ Transplant Patients. In: Journal of Immunotherapy. 2017.
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