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. 2020 Jul 10;12(7):1862.
doi: 10.3390/cancers12071862.

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

David J Pinato  1 , Takahiro Kaneko  1   2 , Anwaar Saeed  3 , Tiziana Pressiani  4 , Ahmed Kaseb  5 , Yinghong Wang  6 , David Szafron  7 , Tomi Jun  8 , Sirish Dharmapuri  8 , Abdul Rafeh Naqash  9 , Mahvish Muzaffar  9 , Musharraf Navaid  9 , Chieh-Ju Lee  10 , Anushi Bulumulle  9 , Bo Yu  11 , Sonal Paul  12 , Neil Nimkar  12 , Dominik Bettinger  13 , Hannah Hildebrand  3 , Yehia I Abugabal  5 , Celina Ang  8 , Thomas U Marron  8 , Uqba Khan  11 , Nicola Personeni  4   14 , Lorenza Rimassa  4   14 , Yi-Hsiang Huang  10
Affiliations

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

David J Pinato et al. Cancers (Basel). .

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.

Keywords: bilirubin; biomarkers; hepatocellular carcinoma; immunotherapy; survival.

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Conflict of interest statement

D.J.P. received lecture fees from ViiV Healthcare, Bayer Healthcare and travel expenses from BMS and Bayer Healthcare; consulting fees for Mina Therapeutics, EISAI, Roche, Astra Zeneca; received research funding (to institution) from MSD, BMS. D.B. has received lecture and speaker fees from Bayer Healthcare and the Falk Foundation Germany. L.R. received lectures fees from AbbVie, Amgen, Eisai, Gilead, Ipsen, Lilly, Roche, Sanofi; advisory board/consulting fees from Amgen, ArQule, AstraZeneca, Basilea, Bayer, Celgene, Eisai, Exelixis, Hengrui, Incyte, Ipsen, Lilly, MSD, Nerviano Medical Sciences, Roche, Sanofi; travel expenses from Ipsen; received research funding (to institution) from Agios, ARMO BioSciences, AstraZeneca, BeiGene, Eisai, Exelixis, Incyte, Ipsen, Lilly, MSD. N.P. received lecture fees from AbbVie and Gilead; travel expenses from ArQule. Y.-H.H has received advisory board/consulting fees for BMS, MSD, Bayer Healthcare, IPSEN, EISAI, Gilead and Lilly. A.S. received research funding (to institution) from AstraZeneca, Exelixis, BMS and Clovis; advisory board/consulting fees from BMS, AstraZeneca, and Exelixis. There are no other personal or financial conflicts of interest to disclose.

Figures

Figure 1
Figure 1
Study flow chart.
Figure 2
Figure 2
The relationship between ALBI grade (A) and Child-Turcotte-Pugh (CTP) class (B) and radiologic disease control by RECIST 1.1 criteria in patients with hepatocellular carcinoma (HCC) treated with immune checkpoint inhibitors (ICI).
Figure 3
Figure 3
Prediction of overall survival by ALBI grade and CTP class in unselected HCC patients treated with ICI (n = 330, A,B) and in patients fulfilling CTP A criteria (n = 239, C). Receiver operating characteristic (ROC) curve analysis demonstrating the role of ALBI, CTP class, and AFP in predicting 90-days mortality from ICI commencement (D). The prognostic role on post-immunotherapy survival (PIOS) of the ALBI grade at the moment of ICI cessation (E).
Figure 3
Figure 3
Prediction of overall survival by ALBI grade and CTP class in unselected HCC patients treated with ICI (n = 330, A,B) and in patients fulfilling CTP A criteria (n = 239, C). Receiver operating characteristic (ROC) curve analysis demonstrating the role of ALBI, CTP class, and AFP in predicting 90-days mortality from ICI commencement (D). The prognostic role on post-immunotherapy survival (PIOS) of the ALBI grade at the moment of ICI cessation (E).
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