Evaluating the safety of immune checkpoint inhibitors prior to liver transplant.
Authors: Aceituno Laia , Magyar Christian Tibor Josef , Tabrizian Parissa , Watt Kymberly , Chascsa David , Schnickel Gabriel , Banz Vanessa , Marino Rebecca , Alconchel Felipe , Martagon Celia , Ruiz-Ortega Lourdes , Moctezuma Carlos , Baker Talia , Nwaduru Chinedu , Castells Luis , O´Kane Grainne , Vogel Arndt , Minguez Beatriz , Sapisochin Gonzalo 
Published: January 2025

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Background:
Liver transplantation (LT) offers a 5-year survival exceeding 70% for selected patients with hepatocellular carcinoma (HCC). Immune checkpoint inhibitors (ICIs) may be used to downstage or bridge to transplantation. This study aims to evaluate the safety of ICIs prior to LT.
Methods:
Multicenter retrospective study, involving 9 centers, included adults who received ICIs and, subsequent LT, between 2019 and 2023. The ICI cohort was matched by age, sex, liver diseases and transplant date (1:3) with a similar cohort of HCC transplanted patients that did not receive ICIs.
Results:
The ICI cohort included 45 patients (Table part 1). The most common underlying liver diseases were viral. 15.5% of patients had macrovascular invasion and, 62.2% multifocal disease. The most commonly used ICI was nivolumab (75.6%), followed by atezolizumab-bevacizumab (17.8%). The median follow up was 32.5 months (17.4 - 47.6). The median ICI duration was 147 days (129.5-276.5), with a median interval of 58 days (22–193) between the last ICI dose and LT. There were 8 (17.8%) cases of graft rejection, 2 steroid-resistant leading to 1 graft failure. There were 4 (8%) HCC recurrences. During follow-up there were 6 deaths, 2 related to HCC recurrence and 4 non liver related. When compared with 135 non-ICI cohort patients, there were no differences within the groups (Table part 2). Importantly, we found no significant differences in crude rejection rates (p=0.5).
Conclusions:
Our study suggest that ICI treatment prior to LT is safe. ICI rejection primarily occurs in the acute post-transplant period (within 3 months), with a low risk of death due to graft failure. Further clinical trials are needed.

Part 1: ICI cohort descriptive analysis. N (%); Median (IQR); Part 2: Comparison between cohorts. N (%); Mean (SD).

(part 1)
ICI-cohort n=45

General data
Male
38 (84.4)

Age
61.2 (7.6)

Etiology of liver diseases
Hepatitis C 17 (37.8)Hepatitis B 6 (13.3)MASLD 6 (13.3)Viral +Alcohol 5 (11.1)Alcohol 3 (6.7)Autoimmune 3 (6.7)Other 3 (6.7)Combined viral 2 (4.4)

Largest tumor (mm)
39 (22)

Macrovascular invasion
7 (15.5)

Multifocal
28 (62.2)

Locoregional therapy
36 (80.0)

Number of locoregional therapies
2 (2)

Immunotherapy
Nivolumab
34 (75.6)

Atezolizumab/bevacizumab
8 (17.8)

Pembrolizumab
1 (2.2)

Nivolumab+pembrolizumab
1 (2.2)

PD1 inhibitor clinical trial
1 (2.2)

Days of ICI treatment
147 (203)

Radiological tumor response ICI
No
17 (37.8)

Transplant
Deceased donor
43 (95.6)

Washout period (days)
58 (171)

Induction therapy (anti-thymoglobulin)
8 (17.8)

Outcomes
Rejection Biopsy proven
8 (17.8) 8 (100)

Time to rejection (days)
43 (102)

Graft failure Rejection
2 (4.4)1 (2.2)

HCC recurrence
4 (8)

Deaths
6 (13.3)

Follow up
Since transplant (months)
32.5 (30.2)

(part 2)

ICI-cohort (n=45)

Non-ICI cohort
(n= 135)

P

Post transplant rejection rate
8 (17.8)
32 (23.7)
0.53

Time to rejection (days)
180.1 (SD 218)
62.2 (SD 62.8)
0.25

Overall deaths
6 (13.3)
10 (7.4)
0.36