Safety and Efficacy of PD-1/PD-L1 Inhibitors in Cancer Patients With Preexisting Autoantibodies

Abstract

BackgroundProgrammed cell death protein-1/programmed cell death ligand-1 (PD-1/PD-L1) inhibitors therapy is now a routine scheme in cancers. However, the effect of preexisting autoantibodies on the safety and efficacy of PD-1/PD-L1 inhibitors in cancer patients is not well understood.MethodsThe present retrospective cohort study evaluated the safety and efficacy of PD-1/PD-L1 inhibitors in patients with preexisting autoantibodies. Patients who received PD-1/PD-L1 inhibitors in the Department of Medical Oncology, Peking Union Medical College Hospital between November 2017 and August 2021 were reviewed.Results67 (37.9%) of the 177 patients, 27 (20.3%) of the 133 patients, and 16 (11.0%) of 146 patients who received PD-1/PD-L1 inhibitors were positive for ANA, anti-Ro52, and antithyroid antibodies, respectively. Preexisting ANA and anti-Ro52 antibody were not associated with the increased risk of immune-related adverse events (irAEs), while thyroid dysfunction was more frequent in patients with positive antithyroid antibody (75.0% versus 13.8%, p < 0.001). The median progression-free survival (PFS, 13.1 versus 7.0 months, p = 0.015) was significantly longer in the ANA-positive patients, while the median overall survival (OS, 14.5 versus 21.8 months, p = 0.67) did not differ significantly between the ANA-positive and ANA-negative groups. Moreover, the preexisting anti-Ro52 and antithyroid antibodies were not significantly associated with PFS and OS.ConclusionsThe presence of ANA and anti-Ro52 antibody were not associated with a higher risk of irAEs, whereas patients positive for antithyroid antibody should monitor closely immune-related thyroid dysfunction. Preexisting ANA might be a predictor of longer PFS, while anti-Ro52 and antithyroid antibodies had no significant effect on survival outcomes in patients receiving PD-1/PD-L1 inhibitors therapy.

Checkpoint inhibitor immune-related adverse events: A focused review on autoantibodies and B cells as biomarkers, advancements and future possibilities

“…Similarly, although De Moel et al ( 106) also recorded an increase in rheumatologic AAbs from baseline in late-stage melanoma patients (who were antibody negative pre-treatment), no association with any irAEs was observed. Several reports have also found no significant association between pre-existing ANAs in various cancer patients prior to ICI therapy, with the occurrence of irAEs (97,99,103,104). Despite the temporal resemblance of classic autoimmune diseases with irAEs, it appears that their mechanisms might be different and whether an increase or decrease in classic rheumatological AAbs is beneficial for the prediction of irAEs remains controversial and requires further investigation.…”

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

“…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 ].…”

“…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 ]. In summary, the evidence is conflicting, and they do not seem to be a reliable predictor for irAE in general when used alone.…”

Longitudinal efficacy and toxicity of SARS-CoV-2 vaccination in cancer patients treated with immunotherapy

“…Recent evidence has focused on the sensitivity of autoantibodies to identify patient risk of developing irAEs when treated with cancer immunotherapy and mainly, immune checkpoint inhibitors [28,29]. Our group has previously utilised and validated a customized auto-antibody panel with the ability to detect a wide range of both IgM and IgG antibodies against 161 self-antigens [30,31].…”