Use of checkpoint inhibitors in liver transplant recipients

Munker, Stefan; Toni, Enrico N. De

doi:10.1177/2050640618774631

Cited by 94 publications

(76 citation statements)

References 20 publications

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“…Immunotherapy using immune checkpoint inhibitors (ICIs), which can interrupt the cancer-immunity cycle and promote the tumor-specific immune cell activity without intrinsic cytotoxicity, has become the standard of care for a variety of tumors, including melanoma, lung cancer, urothelial cancer, kidney cancer, and hepatocellular carcinoma (HCC) [1][2][3][4][5][6][7][8][9][10][11][12]. For HCC patients, increasing importance has been attached to liver transplantation (LT) thanks to the advances in surgical techniques and immunosuppression regimens, resulting in the mean 1-year and 5-year survival rates of 85-90% and 70-75%, respectively [13][14][15][16][17][18].…”

Section: Introductionmentioning

confidence: 99%

Liver graft rejection following immune checkpoint inhibitors treatment: a review

Yang

Sang

2019

Med Oncol

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Immune checkpoint inhibitors (ICIs) have demonstrated remarkable efficacy in a variety of solid tumors; nonetheless, they have not been well investigated and are still recognized as a relative contraindication for patients with a liver transplantation (LT) history, since ICIs treatment might potentially lead to graft rejection. The program death-1 (PD-1) and the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) pathways are implicated in the tolerance of transplanted organ, as well as blockade of the pathways, which contribute to eliminating tumors and may inadvertently lead to peripheral transplant rejection. Currently, no guidelines are available regarding the treatment for ICIs patients with a prior LT history. Therefore, this study was carried out to review the recent studies, attempting to introduce the ICIs-related graft rejection after LT from various aspects. We believed that ICIs could be given for the well-informed patients receiving LT and developed recurrence in a controlled setting. Typically, these patients should be treated according to a clinical care path or a prospective clinical trial, so as obtain a persistent anti-tumor immune response in the meantime of avoiding graft rejection, adjust the immunosuppression, reduce the possibility of graft loss following rejection, and have the opportunity to develop biomarkers for tumor response and transplant rejection.

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Section: Introductionmentioning

confidence: 99%

Liver graft rejection following immune checkpoint inhibitors treatment: a review

Yang

Sang

2019

Med Oncol

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“…One case series correlated PD‐L1 staining of allografts with outcomes after ICI initiation. All 3 patients with positive allograft PD‐L1 staining had severe, and in 2 of the 3 cases, fatal rejection with nivolumab . In light of the findings of Shi et al, this was likely due to baseline subclinical immune activation and/or rejection.…”

Section: Discussionmentioning

confidence: 86%

“…Since 2017, there have been several reports of the use of ICIs, such as nivolumab, in solid organ transplant recipients as an adjuvant therapy for recurrent HCC or melanoma. Many of these reports describe a severe and often fatal alloimmune injury, even when the drug was introduced years after transplant . We present in this case report the first published use of nivolumab in the pretransplant setting for HCC.…”

Section: Introductionmentioning

confidence: 87%

“…alloantigen, cancer, clinical research, dysfunction, editorial, graft survival, hepatology, immune modulation, immune regulation, immunosuppression, liver allograft function, liver transplantation, malignancy, neoplasia: chemotherapy, personal viewpoint, pharmacology, practice describe a severe and often fatal alloimmune injury, even when the drug was introduced years after transplant. [7][8][9][10][11] We present in this case report the first published use of nivolumab in the pretransplant setting for HCC.…”

Section: Introductionmentioning

confidence: 99%

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Fatal hepatic necrosis after nivolumab as a bridge to liver transplant for HCC: Are checkpoint inhibitors safe for the pretransplant patient?

Nordness

Hamel

Godfrey

et al. 2020

American Journal of Transplantation

122

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Nivolumab is an immune checkpoint inhibitor (ICI) currently in phase 3 clinical trials for hepatocellular carcinoma. The safety of ICIs in recipients of organ allotransplant is unclear, and several reports of fatal alloimmune injury after posttransplant ICI use have been published. We present the first published case of nivolumab used in the pretransplant setting for HCC resulting in fatal acute hepatic necrosis in the immediate postoperative period from a profound immune reaction likely propagated by nivolumab. Further investigation and significant caution are needed in the evaluation of patients awaiting transplant who are receiving ICI therapy.

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“…MD Anderson Cancer Center reviewed its institutional data on recipients (N = 39) of various solid organ allograft transplants (kidney, liver, and heart) who developed malignant diseases (melanoma, lung cancer, HCC, cuta-neous squamous cell carcinoma) then received checkpoint inhibitors and found high rates of graft loss (81%) and a high death rate (46%) [51]. Therefore, patients with recurrent HCC after liver transplant should receive immune checkpoint inhibitor treatment with the upmost caution at the risk of rapid organ rejection, as published in multiple case reports [52]. However, there is also a potential to harness the power of checkpoint inhibitor(s) alone or in combination with other agent(s) to amplify the antitumor effects [53].…”

Section: Immune-check Point Inhibitorsmentioning

confidence: 99%

Medical oncology management of advanced hepatocellular carcinoma 2019: a reality check

Lee

2019

Front. Med.

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In terms of global cancer-related deaths, hepatocellular carcinoma (HCC) has the fourth highest mortality rate. Up until 2017, treatment of advanced HCC was largely limited to sorafenib, an oral tyrosine kinase inhibitor, with little to no success in the development of alternative treatment options. However, in the past two years, there has been an unprecedented increase in both the number and type of treatment options available for HCC. As of 2019, the US FDA has approved four oral tyrosine kinase inhibitors, two immune checkpoint inhibitors, and one anti-angiogenesis antibody for the treatment of HCC. Even with this new variety, systemic treatment of advanced HCC remains largely unsatisfactory, and the median survival rate stands at approximately one year. The expected breakthrough of using immune checkpoint inhibitors in advanced HCC did not materialize in 2019. The use of immune checkpoint inhibitors in conjunction with oral tyrosine kinase inhibitors or antiangiogenesis medications is the current clinical research trend, the results of which are eagerly anticipated. Despite limited progress in survival, HCC research is currently experiencing a period of growth and innovation, and there is hope for significant advances in the treatment of advanced HCC as the field continues to develop.

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Use of checkpoint inhibitors in liver transplant recipients

Cited by 94 publications

References 20 publications

Liver graft rejection following immune checkpoint inhibitors treatment: a review

Liver graft rejection following immune checkpoint inhibitors treatment: a review

Fatal hepatic necrosis after nivolumab as a bridge to liver transplant for HCC: Are checkpoint inhibitors safe for the pretransplant patient?

Medical oncology management of advanced hepatocellular carcinoma 2019: a reality check

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