Association of immune-related adverse events induced by nivolumab with a battery of autoantibodies

Abstract

Background The aim of this study was to assess the diagnostic performance of an autoantibody battery in patients receiving immune checkpoint inhibitors who experienced immune-related adverse events (irAEs). Methods We retrospectively analyzed several variables potentially related to irAEs, namely, demographic, clinical, and laboratory characteristics, including an autoantibody battery (antinuclear, anti-neutrophil cytoplasmic, anti-thyroid antibodies and rheumatoid factor). Results Sixty-nine patients (48 men; 61.8 ± 10.9 years at baseline) diagnosed with stage-4 solid-organ cancer and treated with nivolumab were followed up for 12 ± 10.3 months. Thirty-two irAEs were detected in 26 patients (37.5%). Adverse events occurred more commonly in women (62% vs. 27%, p = .006), and younger patients (irAEs: 58.1 ± 9.8, no irAEs: 64.1 ± 10.9 years, p = .024). Autoantibody battery results were available for 26 patients and were more frequently positive in patients with irAEs (87% vs. 30%, p = .009). The positive predictive value, negative predictive value, and diagnostic accuracy of the battery were 82.3%, 77.8%, and 80.8%, respectively. Among the 64 patients with an evaluable response, 23 (38.5%) experienced tumour progression, this being less frequent in patients with irAEs (19% vs. 48.5%, p = .03). Overall survival was higher in patients developing irAEs (HR = 1.88, p = .05). Conclusion Positivity in a readily available autoantibody battery may be associated with the occurrence of irAEs. KEY MESSAGES Positivity in an accessible and inexpensive autoantibody battery including antinuclear, anti-neutrophil cytoplasmic, anti-thyroid antibodies and rheumatoid factor may be associated with the occurrence of immune-related adverse events. Patients with cancer on immune checkpoint inhibitors experiencing immune-related adverse events showed a lower risk of progression and better overall survival than patients not experiencing this type of adverse effect.

Marked, Lasting Disease Regression and Concomitantly Induced Autoimmune Hemolytic Anemia and Hemophagocytic Lymphohistiocytosis in a Patient With Lung Adenocarcinoma and Autoantibodies Receiving Atezolizumab Plus Chemotherapy: A Case Report

“…Autoantibody presence might be associated with a higher rate of irAEs and possibly better survival outcomes in patients with NSCLC and solid-organ cancers who are treated with ICIs. 5 , 6 This is consistent with the severe irAEs and marked, durable response that we observed in our patient after only one cycle of atezolizumab. Nevertheless, the autoantibody type and levels that are associated with ICI safety and efficacy remain unknown.…”

A Systematic Review of the Mechanisms Involved in Immune Checkpoint Inhibitors Cardiotoxicity and Challenges to Improve Clinical Safety

“…Here, we propose different mechanisms related to cardiac irAEs, such as autoantibody production. Autoantibodies induced by ICI therapy include anti-acetylcholine receptors, striated muscle, mitochondria, alanyl-tRNA synthetase, SRP-B, and 3-hydroxy-3-methylglutaryl-coenzyme, these autoantibodies were found too in a recent systematic review published by ( Ghosh et al, 2022 ), and despite that, we did not study the association of ICI-induced autoantibodies and anti-cancer efficacy, where some authors propose that the irAEs are associated with better antitumoral effect or trend for better survival ( de Moel et al, 2019 ; Les et al, 2021 ). Furthermore, the recent finding by Bocksthaler et al, 2021 showed that Troponin I (TnI)-directed autoimmune myocarditis (TnI-AM) is mediated by CD4 + T-cells, and the immunoproteasome is a key player in this autoimmunity.…”

Association between Changes in the Patterns of Antinuclear Autoantibodies during Immune Checkpoint Inhibition Therapy and the Development of Severe Immune Related Adverse Events

“…Second, as in certain autoimmune diseases, some irAEs may be not ANA-related but rather due to cell-mediated immune mechanisms or autoantibody-mediated mechanisms different from ANA [ 35 ]. In line with this second reason, other authors have correlated the presence of autoantibodies with higher irAE rates [ 36 , 37 ], though these studies considered a broader spectrum of different autoantibodies, not specifically ANAs, which may explain the different results.…”