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

The Association Between Albumin Levels and Survival in Patients Treated with Immune Checkpoint Inhibitors: A Systematic Review and Meta-analysis

“…In addition, albumin is a negative acute phase reactant, and its levels decrease in cases of chronic in ammatory states like cancer [71]. While the albumin production could be increased in the early stages of harmful insults like carcinogens, the albumin production is signi cantly decreased in advanced cancer due to malnutrition and the inhibitory pressure of cytokines and chemokines like C-reactive protein and interleukin-6 on the liver [34,53,72]. Therefore, albumin levels could be a biologically plausible biomarker with the potential to re ect both nutritional status and in ammatory pressure of the patients with cancer, and decreased levels of albumin levels could re ect a more advanced cancer stage and a more dismal prognosis.…”

“…In contrast, the data on the association between albumin levels and prognosis is still limited in ICI-treated patients. The available literature on ICI-treated patients is mainly focused on NSCLC cohorts and included only patients with advanced-stage disease [34,52,60], while the ICIs have become standard of care adjuvant treatment options in melanoma [78], NSCLC [79], bladder cancer [80], and esophagus cancer [81]. Additionally, most of the available studies on the prognostic role of albumin levels in ICI-treated patients had limited or absent data regarding the previously established ICI-e cacy biomarkers like PD-L1 and TMB levels [13,82,83].…”

“…More than half of the studies were reported from Far East (n = 15) [32, 39-52], followed by Europe (n = 12) [25,31,37,38,[53][54][55][56][57][58][59][60]]. The 3.5 gr/dL was the most frequently used albumin cut-off in the included studies (n = 20) [25, 31-33, 37, 38, 40-43, 45-52, 54, 56-64], while eight studies evaluated the effect of albumin levels on survival by using albumin as a continuous measure [34,39,44,53,55,[65][66][67]. All but two studies reported HR for OS [25,36,49], while data for PFS was available in the 15 studies [25, 32, 33, 36, 40-42, 48-50, 52, 53, 57, 60, 63, 66].…”

“…The important portion of the heterogeneity were stemmed from the studies including the albumin as a continuous parameter in the analyses. After the exclusion of these studies (n=8) [34,39,44,53,55,[65][66][67], the heterogeneity was decreased to 45% and xed effect meta-analysis after the exclusion of these studies demonstrated a consistent negative effect of low albumin levels on OS (HR: 2.17, 95% CI: 2.00-2.36, p<0.0001) (Figure S2). Sensitivity analyses with the exclusion of individual studies were also demonstrated signi cantly higher risk of death in patients with lower albumin levels.…”

“…Several studies in patients treated with chemotherapy, radiotherapy or targeted therapy demonstrated the higher risk of mortality or progression with lower albumin levels [28][29][30]. Similarly, the albumin levels could be also used for prognosis estimation in ICI-treated patients [31][32][33][34]. However, the data on albumin in ICI-treated patients are limited with heterogeneous patient cohorts, sample sizes and variable cut-offs.…”