Clinical trial NCT05913583: Correlation Between Pre-transplant ICI Exposure and Post-transplant Graft Rejection
Official title: Correlation Between Exposure to Immune Checkpoint Inhibitors Before Liver Transplantation for Hepatocellular Carcinoma and Post-transplant Graft Rejection
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Graft Rejection
Hepatocellular Carcinoma
Immunotherapy
Immune Checkpoint Inhibitor
Keywords: hepatocellular carcinoma
liver transplantation
Immune checkpoint inhibitor
Graft rejection
Lead sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Sponsor class: OTHER
First posted: 2023-06-22
Enrollment: 160
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: A retrospective cohort study will be performed on consecutive HCC patients who underwent LT for HCC. The pretransplant parameters, such as AFP, tumor status, BMI, and etiology et al, as well as posttransplant parameters, such as graft rejection, EAD, hospital death et al, will be analyzed.

Brief summary: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced HCC. The combination of the ICI and other treatment regimens (Anti-VEGF, locoregional therapies et al) produced superior results in patients with advanced-stage HCC compared to those treated with traditional therapeutic regimens. Liver transplantation (LT) offers excellent long-term outcomes for certain patients with HCC. However, the immune-stimulating property of ICIs may lead to rejection and even graft loss, damping their use in treating HCC before liver transplantation. Therefore, it is worthwhile to explore the relationship between exposure to ICIs before LT and the incidence of graft rejection and rejection-related death or graft loss after LT.

Detailed description: This will be a retrospective and observational study, which will analyze the correlation between the use of ICIs and incidences of graft rejection and rejection-related death or graft loss after LT in consecutive recipients with LT for HCC at the Organ Transplantation Center of Sun Yat-sen Memorial Hospital of Sun Yat-sen University.

The primary aim of this study is to analyze the correlation between pretransplant exposure to ICIs and incidences of graft rejection and rejection-related death or graft loss within 1 year after liver transplantation.

The secondary aim is to analyze the risk factors for graft rejection and to explore the correlation between ICI exposure and posttransplantation complication, such as incidences of early allograft dysfunction (EAD), bleeding, infection, biliary and vascular complications et al.

The exploratory aim is to identify potential biomarkers in predicting graft rejection, such as subsets of lymphocytes and cytokines et al.

Eligibility criteria: Inclusion Criteria

1. Written informed consent must be obtained prior to any data collection.
2. Patients must have pathologically or cytologically or by radiological criteria proven hepatocellular carcinoma based on the AASLD practice guidelines.
3. All patients receiving liver transplantation for HCC.

Exclusion Criteria

1. Cholangiocellular carcinoma, combined hepatocellular and cholangiocarcinoma, and other rare types of liver cancer that are confirmed by histology/cytology.
2. Patients with incomplete follow-up data

Primary outcomes:
measure: Graft rejection
timeFrame: 1 year
Secondary outcomes:
measure: Graft loss
timeFrame: 1 year
measure: Hospital death
timeFrame: 1 year
measure: Early allograft dysfunction (EAD)
timeFrame: First 7 days after liver transplantation
Other outcomes:
measure: CD4 to CD8 T cell ratio
timeFrame: 1 year
measure: pDC to mDC ratio
timeFrame: 1 year
Locations:
city: Guangzhou
country: China
facility: Organ Transplantation Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University,
state: Guangdong
Study officials:
affiliation: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
name: Chao Liu, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Schwacha-Eipper B, Minciuna I, Banz V, Dufour JF. Immunotherapy as a Downstaging Therapy for Liver Transplantation. Hepatology. 2020 Oct;72(4):1488-1490. doi: 10.1002/hep.31234. No abstract available.
citation: Tran NH, Munoz S, Thompson S, Hallemeier CL, Bruix J. Hepatocellular carcinoma downstaging for liver transplantation in the era of systemic combined therapy with anti-VEGF/TKI and immunotherapy. Hepatology. 2022 Oct;76(4):1203-1218. doi: 10.1002/hep.32613. Epub 2022 Jul 30.
citation: Katariya NN, Lizaola-Mayo BC, Chascsa DM, Giorgakis E, Aqel BA, Moss AA, Uson Junior PLS, Borad MJ, Mathur AK. Immune Checkpoint Inhibitors as Therapy to Down-Stage Hepatocellular Carcinoma Prior to Liver Transplantation. Cancers (Basel). 2022 Apr 19;14(9):2056. doi: 10.3390/cancers14092056.
citation: Llovet JM, Castet F, Heikenwalder M, Maini MK, Mazzaferro V, Pinato DJ, Pikarsky E, Zhu AX, Finn RS. Immunotherapies for hepatocellular carcinoma. Nat Rev Clin Oncol. 2022 Mar;19(3):151-172. doi: 10.1038/s41571-021-00573-2. Epub 2021 Nov 11.