As we look forward to the bright future of immune checkpoint blockade (ICB) therapy, there is still lacking a pharmacokinetic marker to understand the inter-individual differences in ICB response. ICB therapy is based on IgG antibodies that share the same homeostatic pathway with serum albumin. Therefore, serum albumin level could reflect IgG catabolic rate that directly impacts the clearance of therapeutic IgG antibodies. Through interrogating a large, clinically representative pan-cancer cohort of 1,479 ICB-treated patients, this study found that higher baseline albumin levels were significantly associated with stepwise improvements in overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) (p<0.001), with the variability and reproducibility confirmed in 1,000 bootstrap-resampled cohorts. Furthermore, these findings were also confirmed in most subgroups defined by patient demographics, baseline characteristics, treatments, and cancer types, even in those with low ICB-responsive cancer types and low tumor mutation burden (TMB) (TMB≤10 mut/Mb) that most of which have not been approved by the US Food and Drug Administration (FDA) for ICB therapy. In summary, this study highlights the importance of pretreatment pharmacokinetic modeling for predicting ICB treatment outcomes. Based on serum albumin-an inexpensive, non-invasive, and easily accessible biomarker of IgG pharmacokinetics, we could take a step further towards optimizing ICB therapy.
Keywords: Biomarkers, Tumor; Immunotherapy.
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