Serum Albumin: Early Prognostic Marker of Benefit for Immune Checkpoint Inhibitor Monotherapy But Not Chemoimmunotherapy

Abstract

•Hypoalbuminemia has broadly been viewed as a marker for unfavorable treatment response in advanced cancers, and poor health condition such as cancer-associated cachexia. Decreases in albumin may also correspond to increases of ICI clearance, which has been demonstrated as a potential biomarker for ICI outcomes.•In this single-center retrospective study, we found that low pretreatment albumin, and an albumin decrease of more than 10% from pretreatment within the first or second cycle were strongly associated with short OS in patients with advanced NSCLC treated with ICI monotherapy, but not in patients treated with chemoimmunotherapy.•Our result also showed that such lack of association between albumin and OS in chemoimmunotherapy was even more pronounced among patients with ≥ 1% PD-L1 expression.•Eearly serum albumin change can be incorporated into a holistic model, along with other early biomarkers to better inform outcomes predictions, and early decision-making with ICI monotherapy.•Cancer cachexia may contribute to the association of albumin changes and ICI treatment outcome. However, the underlying mechanism of the observed association in ICI monotherapy but disconnected association in chemoimmunotherapy needs to be further investigated. BackgroundCancer cachexia exhibits decreased albumin and associates with short overall survival (OS) in patients with non–small cell lung cancer (NSCLC), but whether on-treatment albumin changes associate with OS in NSCLC patients treated with immune checkpoint inhibitors (ICIs) and combination chemoimmunotherapy has not been thoroughly evaluated.Patients and MethodsWe conducted a single-center retrospective study of patients with advanced NSCLC who received first-line ICI with or without chemotherapy between 2013 and 2020. The association of pretreatment albumin and early albumin changes with OS was evaluated using Kaplan-Meier method and Cox regression models.ResultsA total of 210 patients were included: 109 in ICI cohort and 101 in ICI + Chemo cohort. Within a median of 21 days from treatment initiation, patients with ≥ 10% of albumin decrease had significantly shorter OS compared to patients without albumin decrease in ICI cohort. Pretreatment albumin and albumin decrease within the first or second cycle of treatment were significantly and independently associated with OS in ICI cohort, but not in ICI + Chemo cohort. The lack of association between albumin and OS with the addition of chemotherapy was more pronounced among patients with ≥ 1% PD-L1 expression in subgroup analysis.ConclusionPretreatment serum albumin and early albumin decrease in ICI monotherapy was significantly associated with OS in advanced NSCLC. Early albumin change, as a routine lab value tested in clinic, may be combined with established biomarkers to improve outcome predictions of ICI monotherapy. The underlying mechanism of the observed association between decreased albumin and ICI resistance warrants further investigation. Cancer cachexia exhibits decreased albumin and associates with short overall survival (OS) in patients with non–small cell lung cancer (NSCLC), but whether on-treatment albumin changes associate with OS in NSCLC patients treated with immune checkpoint inhibitors (ICIs) and combination chemoimmunotherapy has not been thoroughly evaluated. We conducted a single-center retrospective study of patients with advanced NSCLC who received first-line ICI with or without chemotherapy between 2013 and 2020. The association of pretreatment albumin and early albumin changes with OS was evaluated using Kaplan-Meier method and Cox regression models. A total of 210 patients were included: 109 in ICI cohort and 101 in ICI + Chemo cohort. Within a median of 21 days from treatment initiation, patients with ≥ 10% of albumin decrease had significantly shorter OS compared to patients without albumin decrease in ICI cohort. Pretreatment albumin and albumin decrease within the first or second cycle of treatment were significantly and independently associated with OS in ICI cohort, but not in ICI + Chemo cohort. The lack of association between albumin and OS with the addition of chemotherapy was more pronounced among patients with ≥ 1% PD-L1 expression in subgroup analysis. Pretreatment serum albumin and early albumin decrease in ICI monotherapy was significantly associated with OS in advanced NSCLC. Early albumin change, as a routine lab value tested in clinic, may be combined with established biomarkers to improve outcome predictions of ICI monotherapy. The underlying mechanism of the observed association between decreased albumin and ICI resistance warrants further investigation.

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