Immunotherapy in Hepatocellular Cancer Patients with Mild to Severe Liver Dysfunction: Adjunctive Role of the ALBI Grade

David J Pinato,Anwaar Saeed,Takahiro Kaneko,Dominik Bettinger,Sonal Paul,Lorenza Rimassa,David Szafron,Neil Nimkar,Musharraf Navaid,Sirish Dharmapuri,Tiziana Pressiani,Hannah Hildebrand,Yinghong Wang,Thomas U Marron,Anushi Bulumulle,Abdul Rafeh Naqash,Yehia I Abugabal,Mahvish Muzaffar,Uqba Khan,Nicola Personeni,Tomi Jun,Celina Ang,Bo Yu,Ahmed O Kaseb ,Chieh Ju Lee ,Yi Hsiang Huang

doi:10.3390/cancers12071862

Abstract

Immune checkpoint inhibitors (ICI) have shown positive results in patients with hepatocellular carcinoma (HCC). As liver function contributes to prognosis, its precise assessment is necessary for the safe prescribing and clinical development of ICI in HCC. We tested the accuracy of the albumin-bilirubin (ALBI) grade as an alternative prognostic biomarker to the Child-Turcotte-Pugh (CTP). In a prospectively maintained multi-centre dataset of HCC patients, we assessed safety and efficacy of ICI across varying levels of liver dysfunction described by CTP (A to C) and ALBI grade and evaluated uni- and multi-variable predictors of overall (OS) and post-immunotherapy survival (PIOS). We studied 341 patients treated with programmed-death pathway inhibitors (n = 290, 85%). Pre-treatment ALBI independently predicted for OS, with median OS of 22.5, 9.6, and 4.6 months across grades (p < 0.001). ALBI was superior to CTP in predicting 90-days mortality with area under the curve values of 0.65 (95% CI 0.57–0.74) versus 0.63 (95% CI 0.54–0.72). ALBI grade at ICI cessation independently predicted for PIOS (p < 0.001). Following adjustment for ICI regimen, neither ALBI nor CTP predicted for overall response rates or treatment-emerging adverse events (p > 0.05). ALBI grade identifies a subset of patients with prolonged survival prior to and after ICI therapy, lending itself as an optimal stratifying biomarker to optimise sequencing of systemic therapies in advanced HCC.

Highlights

IntroductionThe comparatively poorer prognosis of hepatocellular carcinoma (HCC) with respect to other malignancies derives from the high proportion of patients presenting with advanced disease, the high rates of recurrence following radical treatment of early-stage tumours and the concomitant presence of liver dysfunction, a factor that often limits aggressive treatment [2,3]
Hepatocellular carcinoma (HCC) carries global mortality of over 600,000 cases every year [1].The comparatively poorer prognosis of hepatocellular carcinoma (HCC) with respect to other malignancies derives from the high proportion of patients presenting with advanced disease, the high rates of recurrence following radical treatment of early-stage tumours and the concomitant presence of liver dysfunction, a factor that often limits aggressive treatment [2,3].Sorafenib has for a decade remained the only systemic treatment to offer a survival benefit in advanced HCC [4,5]
Consistent with previously reported evidence, we found the ALBI grade to be significantly associated with a number of features that are predictive of adverse clinical outcome in HCC including more advanced BCLC stage, worse PS and higher AFP levels [34]

Summary

Introduction

The comparatively poorer prognosis of HCC with respect to other malignancies derives from the high proportion of patients presenting with advanced disease, the high rates of recurrence following radical treatment of early-stage tumours and the concomitant presence of liver dysfunction, a factor that often limits aggressive treatment [2,3]. Sorafenib has for a decade remained the only systemic treatment to offer a survival benefit in advanced HCC [4,5]. A number of other molecularly targeted therapies have more recently become available in the management of HCC [9], therapeutic resistance limits long-term survivorship and variable patients’ tolerance to kinase inhibitors influences quality of life and access to second-line therapies [10]

Results

Discussion

Conclusion