Interleukin-7 Risk Allele, Lymphocyte Counts, and Autoantibodies for Prediction of Risk of Immune-Related Adverse Events in Patients Receiving Atezolizumab plus Bevacizumab Therapy for Unresectable Hepatocellular Carcinoma.

Abstract

Atezolizumab plus bevacizumab (AB) therapy was the effective immune checkpoint inhibitor (ICI) for unresectable hepatocellular carcinoma (u-HCC). However, immune-related adverse events (irAEs) are common in patients receiving ICI therapies. Our research aimed to explore the risk factors for irAE development, with attention to interleukin-7 (IL-7) risk alleles, lymphocyte counts, and autoantibodies. Seventy-six patients receiving AB therapy for u-HCC were recruited. Single nucleotide polymorphism genotyping was done for the analysis of rs16906115 polymorphism near IL-7-expressing genes using 20 μL of stored buffy coat at baseline. The association between IL-7 risk alleles, lymphocyte counts, autoantibodies, and irAE development was investigated. irAEs were found in 14 (18%) patients. The incidence of irAEs did not differ significantly between the groups showing IL-7 AG/AA and the GG group (p = 0.72). The incidence in the group with a lymphocyte count of 1,130/µL or more at baseline was higher than in that with a value below 1,130/µL (p = 0.0093). The group showing IL-7 AG/AA or lymphocyte count >1,130/μL had a higher irAE prevalence rate than the others (p = 0.019). IL-7 AG/AA or lymphocyte count >1,130/μL and positivity for autoantibodies at baseline were the prognostic factors for irAE development. irAE incidence could be stratified using a combination of IL-7 AG/AA or lymphocyte counts ≥1,130/µL and positive autoantibodies (p = 0.016). Patients with IL-7 risk alleles, high lymphocyte counts, and autoantibodies at baseline may require careful monitoring for irAE development.