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

Abstract

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.

• Authors: Elise Kang, Mercedes Martinez, Hanna Moisander-Joyce, Yvonne M Saenger, Adam D Griesemer, Tomoaki Kato, Darrell J Yamashiro, Helen Remotti, Robyn D Gartrell
• Journal: Pediatric transplantation (Pediatr Transplant) Vol. 26 Issue 3 Pg. e14209 (05 2022) ISSN: 1399-3046 [Electronic] Denmark
• PMID: 34907641 (Publication Type: Case Reports)
• Copyright: © 2021 Wiley Periodicals LLC.

Chemical References

• Immune Checkpoint Inhibitors
• Ligands

Topics

• Adolescent
• Adult
• Carcinoma, Hepatocellular (surgery)
• Child
• Humans
• Immune Checkpoint Inhibitors
• Ligands
• Liver Neoplasms (drug therapy, surgery)
• Liver Transplantation