Stable liver graft post anti-PD1 therapy as a bridge to transplantation in an adolescent with hepatocellular carcinoma.


Journal

Pediatric transplantation
ISSN: 1399-3046
Titre abrégé: Pediatr Transplant
Pays: Denmark
ID NLM: 9802574

Informations de publication

Date de publication:
05 2022
Historique:
revised: 19 10 2021
received: 16 08 2021
accepted: 29 11 2021
pubmed: 16 12 2021
medline: 23 4 2022
entrez: 15 12 2021
Statut: ppublish

Résumé

Immunotherapy, specifically immune checkpoint inhibitors (ICIs), including anti-programmed cell death 1 (anti-PD1), has recently received clinical approval for the treatment of adult hepatocellular carcinoma (HCC). However, the safety and efficacy of ICIs prior to solid organ transplant are unknown, especially in pediatrics. Safety reports are variable in adults, with some series describing subsequent allograft rejection and loss while others report successful transplants without allograft rejection.As ICIs stimulate the immune system by blocking the interaction between PD1 and the ligand-receptor pair programmed cell death-ligand 1 (PDL1), the downstream effects of T-cell activation increase the risk of graft rejection. Here, we present a case of an adolescent with moderately differentiated non-fibrolamellar HCC treated with pembrolizumab, an anti-PD1 therapy, who subsequently underwent successful orthotopic liver transplantation (OLT). Our patient received an OLT 138 days from the last pembrolizumab dose with graft preservation. The patient has no evidence of recurrent disease or any episode of allograft rejection 48 months post OLT. Staining of tumor and normal tissues from longitudinal specimens finds PDL1 positive Kupffer cells present in normal liver and peritumoral areas with no changes post anti-PD1 therapy. In contrast, tumor cells were negative for PDL1. This case represents a basis for optimism in potential use of anti-PD1 therapy in liver transplant candidates and supports further investigation of immune checkpoint inhibitors use in this unique patient population.

Sections du résumé

BACKGROUND
Immunotherapy, specifically immune checkpoint inhibitors (ICIs), including anti-programmed cell death 1 (anti-PD1), has recently received clinical approval for the treatment of adult hepatocellular carcinoma (HCC). However, the safety and efficacy of ICIs prior to solid organ transplant are unknown, especially in pediatrics. Safety reports are variable in adults, with some series describing subsequent allograft rejection and loss while others report successful transplants without allograft rejection.As ICIs stimulate the immune system by blocking the interaction between PD1 and the ligand-receptor pair programmed cell death-ligand 1 (PDL1), the downstream effects of T-cell activation increase the risk of graft rejection.
METHODS
Here, we present a case of an adolescent with moderately differentiated non-fibrolamellar HCC treated with pembrolizumab, an anti-PD1 therapy, who subsequently underwent successful orthotopic liver transplantation (OLT).
RESULTS
Our patient received an OLT 138 days from the last pembrolizumab dose with graft preservation. The patient has no evidence of recurrent disease or any episode of allograft rejection 48 months post OLT. Staining of tumor and normal tissues from longitudinal specimens finds PDL1 positive Kupffer cells present in normal liver and peritumoral areas with no changes post anti-PD1 therapy. In contrast, tumor cells were negative for PDL1.
CONCLUSION
This case represents a basis for optimism in potential use of anti-PD1 therapy in liver transplant candidates and supports further investigation of immune checkpoint inhibitors use in this unique patient population.

Identifiants

pubmed: 34907641
doi: 10.1111/petr.14209
pmc: PMC9035049
mid: NIHMS1762565
doi:

Substances chimiques

Immune Checkpoint Inhibitors 0
Ligands 0

Types de publication

Case Reports

Langues

eng

Sous-ensembles de citation

IM

Pagination

e14209

Subventions

Organisme : FDA HHS
ID : R01 FD006108
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA013696
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001873
Pays : United States
Organisme : NCATS NIH HHS
ID : KL2 TR001874
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK132710
Pays : United States

Informations de copyright

© 2021 Wiley Periodicals LLC.

Références

Am J Transplant. 2020 Mar;20(3):879-883
pubmed: 31550417
Transplantation. 2021 Jan 1;105(1):67-78
pubmed: 32355121
Lancet Oncol. 2018 Jul;19(7):940-952
pubmed: 29875066
Blood. 2017 Mar 9;129(10):1380-1388
pubmed: 28073785
Expert Opin Drug Metab Toxicol. 2016 Oct;12(10):1247-53
pubmed: 27485741
Am J Transplant. 2021 May;21(5):1979-1980
pubmed: 33316117
Lancet Oncol. 2020 Jan;21(1):121-133
pubmed: 31812554
J Pediatr Surg. 2014 Jan;49(1):166-71; discussion 171
pubmed: 24439603

Auteurs

Elise Kang (E)

Department of Pediatrics, Columbia University Irving Medical Center, New York, New York, USA.

Mercedes Martinez (M)

Department of Pediatrics, Columbia University Irving Medical Center, New York, New York, USA.

Hanna Moisander-Joyce (H)

Department of Pediatrics, Columbia University Irving Medical Center, New York, New York, USA.

Yvonne M Saenger (YM)

Department of Medicine, Columbia University Irving Medical Center, New York, New York, USA.

Adam D Griesemer (AD)

Department of Surgery, Columbia University Irving Medical Center, New York, New York, USA.

Tomoaki Kato (T)

Department of Surgery, Columbia University Irving Medical Center, New York, New York, USA.

Darrell J Yamashiro (DJ)

Department of Pediatrics, Columbia University Irving Medical Center, New York, New York, USA.
Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York, USA.

Helen Remotti (H)

Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York, USA.

Robyn D Gartrell (RD)

Department of Pediatrics, Columbia University Irving Medical Center, New York, New York, USA.

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Classifications MeSH