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

<b><i>Introduction:</i></b> 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. <b><i>Methods:</i></b> 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. <b><i>Results:</i></b> 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 (<i>p</i> = 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 (<i>p</i> = 0.0093). The group showing IL-7 AG/AA or lymphocyte count &gt;1,130/μL had a higher irAE prevalence rate than the others (<i>p</i> = 0.019). IL-7 AG/AA or lymphocyte count &gt;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 (<i>p</i> = 0.016). <b><i>Conclusion:</i></b> Patients with IL-7 risk alleles, high lymphocyte counts, and autoantibodies at baseline may require careful monitoring for irAE development.