Immunotherapy Use Prior to Liver Transplant in Patients with Hepatocellular Carcinoma

Abstract

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related mortality worldwide, and its incidence has increased rapidly in the United States over the past two decades. Liver transplant is considered curative, but is not always possible, and pre-transplant immunotherapy is of great interest as a modality for downstaging the tumor burden. We present a review of the literature on pre-liver transplant immunotherapy use in patients with HCC. Our literature search queried publications in Ovid MEDLINE, Ovid Embase, and Web of Science, and ultimately identified 24 original research publications to be included for analysis. We found that the role of PD-1 and PD-L1 in risk stratification for rejection is of special interest to researchers, and ongoing randomized clinical trials PLENTY and Dulect 2020-1 will provide insight into the role of PD-1 and PD-L1 in liver transplant management in the future. This literature search and the resulting review represents the most thorough collection, analysis, and presentation of the literature on the subject to date.

Transplant oncology – Current indications and strategies to advance the field

“… 215 The half-life of nivolumab and atezolizumab is 27 days and plasma levels typically decline below significant levels after three half-lives, which is why a washout period of 3 months has been suggested. 216 However, reports in the literature are conflicting and the existing evidence mainly consists of case reports and small case series reporting on a heterogenous cohort of patients. 216 In the series reported by Tabrizian et al.…”

“… 216 However, reports in the literature are conflicting and the existing evidence mainly consists of case reports and small case series reporting on a heterogenous cohort of patients. 216 In the series reported by Tabrizian et al. , four of nine patients received their last dose of nivolumab within 14 days of LT, and none of these patients showed any signs of rejection.…”

Laparoscopic Living donor liver transplantation in irresectable intrahepatic cholangiocarcinoma in primary sclerosing cholangitis associated liver cirrhosis

“…With the limited available data, currently no final recommendation can be given regarding the management in this scenario. Given reports of graft rejections after treatment with immunotherapy prior to transplantation and observations that rejections might be more likely in cases with short interval between last application of immunotherapy and transplantation, the literature suggests a waiting period of 4-8 weeks [20].…”

Frontline resection or liver transplantation in patients with single‐nodule hepatocellular carcinoma

“…The question of whether the use of adjuvant immune checkpoint inhibitors before resection or LT would confer additional survival benefits in patients with HCC needs to be elucidated. Several randomized trials are ongoing in this setting 22 and their results are highly anticipated. In the LT setting, where the use of immunotherapy either before or after LT could increase the risk of graft rejection, more preclinical and clinical studies are required to explore the mechanism of the crosstalk of checkpoint inhibitors and immunosuppressive agents to minimize the risk of post‐LT HCC recurrence.…”

“…1 andLimaetal. 18 Immunotherapeutic agents may improve survival in patients withunresectableHCC 20,21 andtheyhavebecomefirst-linethera-piesinadvancedHCC.Thequestionofwhethertheuseofadjuvant immunecheckpointinhibitorsbeforeresectionorLTwouldconfer additional survival benefits in patients with HCC needs to be elucidated.Severalrandomizedtrialsareongoinginthissetting 22…”