Аннотация
Background: Immune checkpoint inhibitors (ICI) have become a new standard of treatment of patients with advanced non-small cell lung cancer (aNSCLC), but 60% of patients are resistant to the therapy. The aim of this study was to investigate the prognostic value of immunological markers in patients with aNSCLC receiving anti-PD-1/PD-L1 antibody.
Methods: The study included 2 groups: group 1- 45 patients receiving ICI in monotherapy in 2 and subsequent lines, group 2- 30 patients receiving first-line chemotherapy. Group 1 was divided into subgroups: response to therapy 6 months (n¼26)
and progression <6 months (n¼19). In both groups there was no history of autoimmune diseases. In group 1, the determination of HLA-DRB1, neopterin (NPT), beta2-microglobulin (B2-MG), autoantibodies, IL-6, IL-18 was carried out after 2 months of starting therapy, and in group 2 this was done before the start of the next cycle of a platinum-based doublet.
Results: In patients in group 2, no autoantibodies were detected, and the level of B2-MG and NPT was lower than in patients in group1 (p <0.0001). In group 1, the level of B2-MG was lower in patients with a duration of response to ICI 6 months, than in patients with progression <6 months: median was 1.7 mg/L and 2.9 mg/L, respectively (p <0.0001). Progression-free survival (PFS) was lower in patients receiving ICI with high level of B2-MG (2.5 mg/L) than in patients with B2-MG <2.5 mg/L: 168 days and not reached, respectively (p ¼ 0.017). The level of NPT was lower in patients with response 6 months than in those with disease progression <6 months: 8.6 nmol/L and 13.4 nmol/L, respectively (p <0.0001). PFS was shorter in patients with NPT 12 nmol/L than in patients with NPT <12 nmol/L: 164 days and not reached, respectively (p ¼ 0.0007). HLA-DRB1*03 and anti-TPO was associated with response 6 months (p ¼ 0.0156 for each marker). HLA-DRB1*03 was associated with longer PFS compared with other allelic variants: not reached versus 224 days, respectively (p¼ 0.028). Higher levels of IL-6 and IL-18 were observed in patients receiving ICI with early progression than in patients with a response of 6 months and in patients in the comparison group (p ¼ 0.001 and p <0.0001, respectively).
Conclusions: Immunological markers allow prediction of response to ICI in patients with aNSCLC.