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

Abstract

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 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 any preexisting 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.This article is protected by copyright. All rights reserved.

Non-Invasive Predictive Biomarkers for Immune-Related Adverse Events Due to Immune Checkpoint Inhibitors

“…Autoantibodies are one of the most well-studied predictive biomarkers for irAEs. Several studies have shown that a pre-existing collection of autoantibodies such as antinuclear antibody, rheumatoid factor, or antithyroid antibodies (antithyroglobulin, and antithyroid peroxidase) before ICI treatment is associated with increased irAEs [ 11 , 12 , 13 , 14 ].…”

“…However, the results were somewhat inconsistent when investigating which specific autoantibody was the main contributor to the association with irAEs. The most promising and well-studied autoantibody was anti-nuclear antibody [ 14 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 ], followed by rheumatoid factor [ 13 , 22 ], both studied in multiple types of solid tumors, including malignant melanoma and NSCLC. Some studies suggested a positive association between pre-existing autoantibodies and the development of any irAE [ 14 , 16 , 17 , 18 , 19 ], but some reported no association [ 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 ].…”

Changes in serum tumor marker levels are efficient predictors of complete response in patients with unresectable hepatocellular carcinoma treated with atezolizumab plus bevacizumab

“…Currently, tumor markers, neutrophil to lymphocyte ratio, biomarkers, and imaging ndings are reported as factors that may predict overall responses. [4][5][6][7][8][9][10][11] However, predicting factors speci c to CR remains unclear.…”

Pathologically successful conversion hepatectomy for advanced giant hepatocellular carcinoma after multidisciplinary therapy: A case report and review of literature

“…Several liver diseases, such as hepatitis virus infection, alcoholism, and nonalcoholic fatty liver disease, are often associated with the development of HCC[ 3 - 5 ]. When diagnosed, more than 80% of patients are in the advanced stage when they are diagnosed and have obvious resistance to conventional chemotherapy and radiotherapy[ 6 - 8 ].…”