scholarly journals Neoadjuvant Programmed Cell Death 1 (PD-1) Inhibitor Treatment in Patients With Hepatocellular Carcinoma Before Liver Transplant: A Cohort Study and Literature Review

2021 ◽  
Vol 12 ◽  
Author(s):  
Zi-yun Qiao ◽  
Zi-jie Zhang ◽  
Zi-cheng Lv ◽  
Huan Tong ◽  
Zhi-feng Xi ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Literature Review ◽  
Liver Transplant ◽  
Disease Control ◽  
Objective Response ◽  
Disease Control Rate ◽  
Transplant Recipients ◽  
Programmed Cell Death 1

Programmed cell death 1 (PD-1) blockade is considered contraindicated in liver transplant (LT) recipients due to potentially lethal consequences of graft rejection and loss. Though post-transplant PD-1 blockade had already been reported, pre-transplant use of PD-1 blockade has not been thoroughly investigated. This study explores the safety and efficacy of neoadjuvant PD-1 blockade in patients with hepatocellular carcinoma (HCC) after registration on the waiting list. Seven transplant recipients who underwent neoadjuvant PD-1 blockade combined with lenvatinib and subsequent LT were evaluated. The objective response rate (ORR) and disease control rate (DCR) was 71% and 85% according to the mRECIST criteria. Additionally, a literature review contained 29 patients were conducted to summarize the PD-1 blockade in LT for HCC. Twenty-two LT recipients used PD-1 inhibitors for recurrent HCC. 9.1% (2/22) and 4.5% (1/22) recipients achieved complete remission (CR) and partial remission (PR), respectively; 40.9% (9/22) recipients had progressive disease (PD). Allograft rejection occurred in 45% of patients. In total, seven patients from our center and three from the literature used pretransplant anti-PD-1 antibodies, eight patients (80%) had a PR, and the disease control rate was 100%. Biopsy-proven acute rejection (BPAR) incidence was 30% (3 in 10 patients), two patients died because of BPAR. This indicated that neoadjuvant PD-1-targeted immunotherapy plus tyrosine kinase inhibitors (TKI) exhibited promising efficacy with tolerable mortality in transplant recipients under close clinical monitoring.

scholarly journals Genetic variants of programmed cell death 1 are associated with HBV infection and liver disease progression

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Nghiem Xuan Hoan ◽  
Pham Thi Minh Huyen ◽  
Mai Thanh Binh ◽  
Ngo Tat Trung ◽  
Dao Phuong Giang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Death ◽  
Liver Disease ◽  
Programmed Cell Death ◽  
Disease Progression ◽  
Infection Risk ◽  
Hbv Infection ◽  
Liver Disease Progression ◽  
Increased Risk ◽  
Programmed Cell Death 1

AbstractThe inhibitory effects of programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) modulates T-cell depletion. T-cell depletion is one of the key mechanisms of hepatitis B virus (HBV) persistence, in particular liver disease progression and the development of hepatocellular carcinoma (HCC). This case–control study aimed to understand the significance of PD-1 polymorphisms (PD-1.5 and PD-1.9) association with HBV infection risk and HBV-induced liver disease progression. Genotyping of PD-1.5 and PD-1.9 variants was performed by direct Sanger sequencing in 682 HBV-infected patients including chronic hepatitis (CHB, n = 193), liver cirrhosis (LC, n = 183), hepatocellular carcinoma (HCC, n = 306) and 283 healthy controls (HC). To analyze the association of PD-1 variants with liver disease progression, a binary logistic regression, adjusted for age and gender, was performed using different genetic models. The PD-1.9 T allele and PD-1.9 TT genotype are significantly associated with increased risk of LC, HCC, and LC + HCC. The frequencies of PD-1.5 TT genotype and PD-1.5 T allele are significantly higher in HCC compared to LC patients. The haplotype CT (PD-1.5 C and PD-1.9 T) was significantly associated with increased risk of LC, HCC, and LC + HCC. In addition, the TC (PD-1.5 T and PD-1.9 C) haplotype was associated with the risk of HCC compared to non-HCC. The PD-1.5 CC, PD-1.9 TT, genotype, and the CC (PD-1.5 C and PD-1.9) haplotype are associated with unfavorable laboratory parameters in chronic hepatitis B patients. PD-1.5 and PD1.9 are useful prognostic predictors for HBV infection risk and liver disease progression.

scholarly journals Evaluation of the Association between Programmed Cell Death-1 Gene Polymorphisms and Hepatocellular Carcinoma Susceptibility in Turkish Subjects. A Pilot Study

2020 ◽  
Author(s):  
Abdullah Fatih Demirci ◽  
Coskun Ozer Demirtas ◽  
Fatih Eren ◽  
Demet Yilmaz ◽  
Caglayan Keklikkiran ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Turkish Population ◽  
Control Group ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Programmed Cell Death 1 ◽  
Significant Difference ◽  
And Control

Background and Aims: Programmed cell death-1 (PD-1) has a vital role in regulating T-cell function, and immune escape mechanism of cancer cells. It was shown that there could be a relationship between single nucleotide polymorphisms (SNPs) in the PD-1 gene and susceptibility to hepatocellular carcinoma (HCC) based on various studies. We aimed to investigate the role of three SNPs within the PD-1 gene in susceptibility to HCC in the Turkish population. Methods: Single nucleotide polymorphisms of PD-1.1, 1.5, and 1.6 were genotyped by using TaqMan Allelic Discrimination Assays in blood samples of 137 HCC and 136 control subjects, matched for age and gender. The genotype, allele and haplotype frequencies were compared in HCC and control groups using logistic regression analysis. Results: Genotype distributions of PD-1.1, PD-1.5 and PD-1.6 SNPs were in Hardy-Weinberg equilibrium. No significant difference was observed in the genotype distribution of PD-1.1, PD-1.5 and PD-1.6 polymorphisms among gender and age-matched HCC (M/F: 96/41; mean age: 61.4 ±11.7 years) and control group (M/F: 94/42; mean age: 61.4±10.1). In the haplotype analysis of PD-1.1/PD-1.5/PD-1.6, no significant difference was found among HCC and control group adjusted for sex and age (all p values>0.1). Conclusion: Our findings, firstly reporting the association of PD-1.5 polymorphism with HCC, and PD-1.1 and PD-1.6 with HCC in the Turkish population, suggest that PD-1 polymorphisms are not predisposing factors for HCC development. Future studies with larger sample sizes and different ethnic populations are required to validate our findings.

scholarly journals A Case of Poorly Differentiated Hepatocellular Carcinoma, Lymphocyte-rich.

2021 ◽  
Author(s):  
Ginji Omori ◽  
Takahiro Osuga ◽  
Koji Miyanishi ◽  
Kota Hamaguchi ◽  
Shingo Tanaka ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Programmed Cell Death 1 ◽  
Poorly Differentiated ◽  
Inhibitor Treatment

A 70-year-old woman was diagnosed poorly differentiated hepatocellular carcinoma (HCC), lymphocyte rich. In this case, programmed cell death 1 expression was observed. Immune checkpoint inhibitor treatment may be effective in such cases, although there have been no reports of their use for poorly differentiated HCC, lymphocyte-rich.

Programmed Cell Death 1 (PD-1) Ligand (PD-L1) Expression in Solid Tumors As a Predictive Biomarker of Benefit From PD-1/PD-L1 Axis Inhibitors: A Systematic Review and Meta-Analysis

2017 ◽  
pp. 1-15 ◽  
Author(s):  
Monica Khunger ◽  
Adrian V. Hernandez ◽  
Vinay Pasupuleti ◽  
Sagar Rakshit ◽  
Nathan A. Pennell ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Solid Tumors ◽  
Immune Cell ◽  
Meta Analysis ◽  
Objective Response ◽  
Small Cell Lung ◽  
Programmed Cell Death 1 ◽  
Tumor Types

Purpose Drugs targeting the programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathway show significant clinical activity across several tumor types. However, a majority of patients do not respond to these agents. Use of biomarker assays to predict response to these agents is an active area of research; however, the predictive value of PD-L1 immunohistochemistry (IHC) assays is largely inconsistent across clinical trials. In this meta-analysis of clinical trials of PD-1/PD-L1–targeted agents, we evaluate the predictive value of a tumor and tumor-infiltrating immune cell PD-L1 IHC assay as a biomarker for objective response to PD-1/PD-L1 inhibitors. Methods We searched databases (PubMed, Medline, ASCO abstracts, European Society for Medical Oncology abstracts, and Scopus) up until December 2016 for clinical trials using PD-1/PD-L1 inhibitors with reported PD-L1 biomarker data. Objective response rates (primary end point) from all phase I to III trials investigating nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab in advanced solid tumors were collected. Odds ratios (ORs) for response in PD-L1–positive patients compared with PD-L1–negative patients were calculated using the DerSimonian-Laird random effects model to combine trials. We performed meta-analysis as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Results Forty-one distinct trials with 6,664 patients were identified. PD-L1 expression was predictive of favorable response across all tumor types (OR, 2.26; 95% CI, 1.85 to 2.75; P < .001), with the significantly largest effect observed in non–small-cell lung cancer (OR, 2.51; 95% CI, 1.99 to 3.17; P < .001). A subgroup analysis across all non–small-cell lung cancer trials using nivolumab and Dako clone 28-8 (Dako, Carpinteria, CA) IHC antibody assay yielded a significantly higher objective response rate in patients with tumor PD-L1 expression even at the minimum cutoff value of 1% (OR, 2.17; 95% CI, 1.03 to 4.57). Conclusion Our meta-analysis shows that tumor and tumor-infiltrating immune cell PD-L1 overexpression based on IHC is associated with significantly higher response rates to PD-1/PD-L1 axis inhibitors across a range of malignant solid tumors.

Lenvatinib plus pembrolizumab versus lenvatinib in patients with unresectable hepatocellular carcinoma: A real world study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16138-e16138
Author(s):  
I-Cheng Lee ◽  
Chi-Jung Wu ◽  
San-Chi Chen ◽  
Yee Chao ◽  
Yi-Hsiang Huang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Disease Control ◽  
Real World ◽  
Objective Response Rate ◽  
Response Rate ◽  
Objective Response ◽  
Progression Free Survival ◽  
Disease Control Rate ◽  
Recist 1.1 ◽  
Unresectable Hepatocellular Carcinoma

e16138 Background: The combination of lenvatinib (LEN) and pembrolizumab (PEMBRO) showed promising response rates and survival in a phase 1b trial for patients with unresectable hepatocellular carcinoma (HCC). Whether LEN plus PEMBRO provides better outcomes than LEN monotherapy remains unclear. The aim of this study was to compare the outcomes of LEN plus PEMBRO versus lenvatinib monotherapy in patients with unresectable HCC in the real world setting. Methods: A total of 123 patients with unresectable HCC were retrospectively enrolled, including 61 patients with LEN monotherapy and 62 patients with LEN plus PEMBRO. We evaluated progression-free survival (PFS), overall survival (OS), objective response rate (ORR) and disease control rate (DCR) by RECIST 1.1 and modified RECIST (mRECIST) criteria. Results: One hundred and one (82.1%) patients were in BCLC stage C and 81 (65.9%) patients received LEN or LEN plus PEMBRO as first line setting. During a median follow-up period of 8.0 months, 71 (57.7%) and 31 (25.2%) of patients had disease progression and death, respectively. The median PFS was 8.4 and 4.9 months in the LEN plus PEMBRO and LEN monotherapy groups, respectively (p = 0.033). The median OS was not reached in the LEN-PEM group and was 17.2 months in the LEN monotherapy group (p = 0.064). Patients with LEN plus PEMBRO had higher objective response rate (ORR: 34.4% vs 23.7% by RECIST 1.1, p = 0.277; 57.4% vs 32.2% by mRECIST, p = 0.010) and higher disease control rate (83.6% vs 62.7% by RECIST 1.1, p = 0.017; 85.2% vs 62.7% by mRECIST, p = 0.009). In subgroup patients with BCLC stage C, LEN plus PEMBRO provided significantly longer PFS (9.1 vs 4.8 months, p = 0.008), higher ORR (60% vs 33.3%, p = 0.015) and higher DCR (88% vs 60.4%, p = 0.004) by mRECIST criteria. Conclusions: LEN plus PEMBRO provides significantly better ORR, DCR and PFS then LEN monotherapy for patients with unresectable HCC.

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