The clinical utility of comprehensive measurement of autoimmune disease-related antibodies in patients with advanced solid tumors receiving immune checkpoint inhibitors: a retrospective study

Izawa, Naoki; Shiokawa, Hisae; Onuki, Risa; Hamaji, Koki; Morikawa, Kei; Saji, Hisashi; Ohashi, Hiroyuki; Kasugai, Shigeru; Hayakawa, Nozomi; Ohara, Tatsuru; Sunakawa, Yu

doi:10.1016/j.esmoop.2022.100415

Cited by 10 publications

(8 citation statements)

References 18 publications

(27 reference statements)

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“…Further studies of the relationship between preexisting psoriasis and the subtype of underlying irAEs are warranted. What is more, greater research into AID-related antibodies (Abs) is needed to predict irAEs such as anti-thyroglobulin (Tg) and anti-thyroid peroxidase (TPO) Abs (42,43).…”

Section: Discussionmentioning

confidence: 99%

Immune Checkpoint Inhibitors in the Treatment of Patients With Cancer and Preexisting Psoriasis: A Systematic Review and Meta-Analysis of Observational Studies

Zhou

Zhang

et al. 2022

Front. Oncol.

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BackgroundImmunotherapies represented by immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment. A large part of the population has both cancer and psoriasis but is usually excluded from ICI clinical trials because of the dysregulated activation of the immune system. This is the first study to evaluate the safety and efficacy of ICI therapy in patients with cancer and preexisting psoriasis.MethodsPubMed, EMBASE, Cochrane, and MEDLINE databases were searched from inception through February 2022. Observational studies on patients with cancer and confirmed psoriasis before ICI initiation were included. Outcomes included the incidence of psoriasis flares, de novo immune-related adverse events (irAEs), discontinuation rate due to flare/de novo irAEs, and efficacy of ICI therapy. Clinical manifestations, management, and outcomes for adverse events (AEs) were systematically reviewed. All pooled analyses were based on a random-effects model using Stata software. Meta-regression and subgroup analyses were performed to identify sources of heterogeneity.ResultsTwelve studies involving 191 patients were included. The pooled incidence of psoriasis flares was 45.0% (95% CI: 31.1%-58.9%, I2 = 71.7%) and 44.9% (95% CI: 29.0%–60.7%, I2 = 71.8%) for de novo irAEs. The tumor type, psoriasis subtype, ICI class, and country were the main sources of heterogeneity. Grade 3–4 flares occurred in 10.8% (95% CI: 5.3%–16.3%) of patients, and about 16.6% (95% CI: 10.7%–22.5%) of patients experienced grade 3–4 de novo irAEs. The estimated incidence of ICI discontinuation due to AE was 18.5% (95% CI: 6.1%–30.8%, I2 = 68.7%). The median times to develop flare and de novo irAEs were 44 and 63 days, respectively. Endocrinopathies and colitis were the most common de novo irAEs. Conventional therapy is effective for most AEs. The estimated objective response rate (ORR) of ICIs was 38.1% (95% CI: 11.8%–64.3%, I2 = 81.7%), and the disease control rate (DCR) was 64.5% (95% CI: 55.3%–73.8%, I2 = 0).ConclusionsThe flare of patients with cancer and preexisting psoriasis treated with ICI therapy is frequent, but the incidence of de novo irAEs and the efficacy of ICI therapy are comparable to those of the general population. Most AEs are mild and manageable with conventional therapy, which required discontinuation of ICI therapy in 18.5%.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42022320646

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Section: Discussionmentioning

confidence: 99%

Immune Checkpoint Inhibitors in the Treatment of Patients With Cancer and Preexisting Psoriasis: A Systematic Review and Meta-Analysis of Observational Studies

Zhou

Zhang

et al. 2022

Front. Oncol.

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“…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 ].…”

Section: Biomarkersmentioning

confidence: 99%

“…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.…”

Section: Biomarkersmentioning

confidence: 99%

“…In seven studies, the presence of pre-ICI treatment antithyroid antibodies (either antithyroglobulin or antithyroid peroxidase) was associated with thyroid dysfunction [ 14 , 26 , 89 , 90 , 91 , 92 , 93 ]. Several studies further investigated antithyroid antibodies and revealed that the levels of both antithyroid antibodies in pretreatment and post-treatment settings were associated with an increased risk of thyroid dysfunction [ 23 , 94 , 95 , 96 , 97 , 98 , 99 ]. Interestingly, a cohort of patients with NSCLC who received pembrolizumab and developed hypothyroid irAEs exhibited a common thyroid function trajectory of initial transient hyperthyroidism within 1–2 months after pembrolizumab therapy, followed by prolonged hypothyroidism [ 93 ].…”

Section: Biomarkersmentioning

confidence: 99%

“…Other biomarkers that have been reported to be associated with pneumonitis included HLA-B35, especially HLA-B*35:01, HLA-DRB1*11, and pre-existing anti-glutamic acid decarboxylase (anti-GAD) [ 23 , 34 , 122 ]. Interestingly, in a multivariate analysis, PD-L1 TPS was not significantly associated with pneumonitis in patients with NSCLC who received anti-PD(L)1 monotherapy [ 28 ].…”

Section: Biomarkersmentioning

confidence: 99%

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

Ponvilawan,

Khan,

Subramanian

et al. 2024

Cancers

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Immune-related adverse events (irAEs) are the most common complication of immune checkpoint inhibitor (ICI) therapy. With the widespread use of ICIs in patients with solid tumors, up to 40% of the patients develop irAEs within five months of treatment, and 11% develop severe irAEs requiring interventions. A predictive test for irAEs would be a crucial tool for monitoring for complications during and after ICI therapy. We performed an extensive review of potential predictive biomarkers for irAEs in patients who received ICI therapy. Currently, only thyroid-stimulating hormone is utilized in common clinical practice. This is due to the unavailability of commercial tests and unclear predictive values from various studies. Given the lack of single strong predictive biomarkers, some novel approaches using composite scores using genomic, transcriptomics, cytokine levels, or clinical parameters appear appealing. Still, these have yet to be validated and incorporated into clinical practice. Further research conducted to validate the models before implementing them into real-world settings will be of the utmost importance for irAE prediction.

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Immune-related thyroid dysfunctions during anti PD-1/PD-L1 inhibitors: new evidence from a single centre experience

et al. 2023

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The clinical utility of comprehensive measurement of autoimmune disease-related antibodies in patients with advanced solid tumors receiving immune checkpoint inhibitors: a retrospective study

Cited by 10 publications

References 18 publications

Immune Checkpoint Inhibitors in the Treatment of Patients With Cancer and Preexisting Psoriasis: A Systematic Review and Meta-Analysis of Observational Studies

Immune Checkpoint Inhibitors in the Treatment of Patients With Cancer and Preexisting Psoriasis: A Systematic Review and Meta-Analysis of Observational Studies

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

Immune-related thyroid dysfunctions during anti PD-1/PD-L1 inhibitors: new evidence from a single centre experience

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