Significance of the autoantibody assay in predicting the development of immune-related adverse events in patients receiving atezolizumab plus bevacizumab combination therapy for unresectable hepatocellular carcinoma

AimAtezolizumab plus bevacizumab (AB) combination therapy is the first-line treatment for unresectable hepatocellular carcinoma (u-HCC). The management of immune-related adverse events (irAEs) is an important issue associated with achieving a good therapeutic response in patients receiving AB therapy. However, few studies have reported irAE development in patients receiving AB therapy. This study focused on the association between irAE development and autoantibodies at baseline in patients receiving AB therapy.MethodsSixty-one patients receiving AB therapy were enrolled. For autoantibodies, the following antibodies were tested before the start of AB therapy: antinuclear antibodies, rheumatoid factor (RF), anti-thyroglobulin antibodies, thyroid peroxidase antibodies, anti-thyroid stimulating hormone receptor antibodies, and acetylcholine receptor antibodies. A patient was considered to have pre-existing antibodies if any of the listed antibodies were present at baseline.ResultsTen patients (16%) developed irAEs during the observation period. The irAEs included liver injury, hypothyroidism, adrenal insufficiency, adrenocorticotropic hormone deficiency, and rhabdomyolysis. Patients with irAE (n = 10) were more likely to be positive for any autoantibody (hazard ratio [HR] 3.7, p = 0.047) and RF at baseline (HR 5.4, p = 0.035) and to achieve complete response (HR 5.8, p = 0.027) than those without. The presence of autoantibodies at baseline was an independent factor associated with irAE development.ConclusionIn the real world, 16% of patients receiving AB therapy for u-HCC developed irAEs. Patients with autoantibodies at baseline are at high risk of developing irAEs and require cautious follow-up. It may be difficult to continue atezolizumab plus bevacizumab (AB) combination therapy for unresectable hepatocellular carcinoma (u-HCC) in patients with severe immune-related adverse events (irAEs), and it may lead to deterioration of their general condition. Therefore, it is important to establish a system for predicting the risk of irAE development before starting AB therapy. Several studies have reported that the presence of autoantibodies at baseline may be associated with irAE development in patients with other types of carcinomas. The present study aimed to determine the association between autoantibodies and irAE development in patients receiving AB therapy for u-HCC. Sixteen percent of patients developed irAEs during the observation period. Autoantibodies at baseline was an independent factor associated with irAE development (hazard ratio: 3.7, p = 0.047). Patients with autoantibodies at baseline are at high risk of irAE development and require cautious follow-up.image