Prognostic significance of pre-treatment ALBI grade in advanced non-small cell lung cancer receiving immune checkpoint therapy

Abstract

The liver is an essential organ for regulating innate and acquired immunity. We hypothesized that the pre-treatment hepatic function affects the clinical outcome of immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC). We analyzed 140 patients with NSCLC who received ICIs. We investigated the association between pre-treatment liver function, assessed using the albumin–bilirubin (ALBI) grade, and clinical outcomes in univariate, multivariate, and propensity score matching analyses. Patients were divided into four grades according to pre-treatment liver function. Eighty-eight patients had good hepatic reserve (ALBI grade 1 or 2a), whereas 52 patients had poor hepatic reserve (ALBI grade 2b or 3). In the univariate Kaplan–Meier analysis, the ALBI grade 1, 2a group had a significantly prolonged progression-free survival (PFS, 5.3 versus 2.5 months, p = 0.0019) and overall survival (OS, 19.6 vs. 6.2 months, p = 0.0002). These results were consistent, regardless of whether the analysis was performed in patients with a performance status of 0 or 1 at pre-treatment (N = 124) or in those selected using propensity score matching (N = 76). In the multivariate analysis, pre-treatment ALBI grade was an independent prognostic factor for both PFS (hazard ratio [HR] 0.57, 95% confidence interval [95% CI] 0.38–0.86, p = 0.007) and OS (HR 0.45, 95% CI 0.29–0.72, p = 0.001). Our results suggest that pre-treatment hepatic function assessed by ALBI grade could be an essential biomarker for predicting the efficacy of treatment with ICIs in NSCLC.

Prognostic significance of pretreatment albumin-bilirubin (ALBI) grade and platelet-albumin-bilirubin (PALBI) grade in patients with small cell lung cancer

“…In later studies, these grades were also associated with the prognosis of HCC. Subsequently, these grades were found to be related to prognosis in pancreatic cancer with liver metastasis, operated gastric cancer, cholangiocellular carcinoma, and non-small cell lung cancer [17][18][19][20].…”

The ALBI score: From liver function in patients with HCC to a general measure of liver function

“… Matsukane et al. 133 Retrospective 140 Non-small cell lung cancer ALBI grade was an independent prognostic factor for both progression-free survival and overall survival who received immune checkpoint inhibitors. Takada et al.…”

“…For example, ALBI has been shown to be prognostic in cancers other than HCC, including pancreatic, colon and gastric cancer, intrahepatic cholangiocarcinoma, extrahepatic bile duct cancer, and even brain cancer (glioma and medulloblastoma). [114] , [115] , [116] , [117] , [118] , [119] , [120] , [121] , [122] , [123] , [124] , [125] , [126] , [127] , [128] , [129] , [130] , [131] , [132] , [133] , [134] , [135] , [136] ALBI is likely to be reflective of liver dysfunction in patients undergoing hepatic resection for intrahepatic tumours, such as intrahepatic cholangiocarcinoma or metastatic liver tumours, and tolerance for those undergoing systemic therapy, including chemotherapies, molecular-targeted drugs and immune checkpoint inhibitors. 118 , 123 , [126] , [127] , [128] , 131 , 133 , 134 Although most authors have attempted to link the association of ALBI with a particular cancer to liver function, we should consider whether its association with mortality is actually through some aspect of liver dysfunction or whether it simply reflects the prognostic power of serum albumin and bilirubin levels, independent of liver function.…”

“… [114] , [115] , [116] , [117] , [118] , [119] , [120] , [121] , [122] , [123] , [124] , [125] , [126] , [127] , [128] , [129] , [130] , [131] , [132] , [133] , [134] , [135] , [136] ALBI is likely to be reflective of liver dysfunction in patients undergoing hepatic resection for intrahepatic tumours, such as intrahepatic cholangiocarcinoma or metastatic liver tumours, and tolerance for those undergoing systemic therapy, including chemotherapies, molecular-targeted drugs and immune checkpoint inhibitors. 118 , 123 , [126] , [127] , [128] , 131 , 133 , 134 Although most authors have attempted to link the association of ALBI with a particular cancer to liver function, we should consider whether its association with mortality is actually through some aspect of liver dysfunction or whether it simply reflects the prognostic power of serum albumin and bilirubin levels, independent of liver function. The mechanism underlying the prognostic impact of albumin and bilirubin remains unknown, but authors of the aforementioned studies have discussed the role of albumin as an indicator of malnutrition, and the immunomodulatory roles of both albumin and bilirubin.…”

Blood Biomarkers of Response to Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer

“…The ALBI (Albumin-Bilirubin) score is calculated using the serum albumin and bilirubin levels and is divided into four grades. In a retrospective study with 140 NSCLC patients treated with ICIs, the subgroup with good hepatic reserve (ALBI grade 1–2a) had a significantly superior progression-free survival (PFS) and overall survival (OS) compared with the subgroup with poor hepatic reserve (ALBI grade 2b or 3) (PFS, 5.3 versus 2.5 months, p = 0.0019 and OS, 19.6 vs. 6.2 months, p = 0.0002) [ 51 ].…”