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

Our plain-English summary of The clinical utility of comprehensive measurement of autoimmune disease-related antibodies in patients with advanced solid tumors receiving immune checkpoint inhibitors: a retrospective study, by N. Izawa, H. Shiokawa, R. Onuki, et al (ESMO Open, 2022).

The study

• Authors: N. Izawa, H. Shiokawa, R. Onuki, K. Hamaji, K. Morikawa, H. Saji, H. Ohashi, S. Kasugai, N. Hayakawa, T. Ohara, Y. Sunakawa
• Journal: ESMO Open
• Published: 2022;7(2):100415
• Cited by: 18 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: The comprehensive measurement of autoimmune disease-related antibodies (Abs) before immune checkpoint inhibitor (ICI) treatment may be useful for predicting the development of immune-related adverse events (irAEs); however, the clinical utility is not well known.

Materials And Methods: We retrospectively analyzed patients with advanced solid tumors treated with ICI monotherapy or doublet combination therapy between July 2014 and December 2020 at single institute. Anti-nuclear antibody (ANA), anti-thyroglobulin (Tg) Ab, anti-thyroid peroxidase (TPO) Ab, anti-glutamic acid decarboxylase (GAD) Ab, anti-acetylcholine esterase receptor (AchR) Ab, and platelet-associated immunoglobulin G (PA-IgG) Ab were comprehensively measured for the screening before ICI therapy.

Results: Of 275 registered patients (median age, 70 years; male, 64.4%; Eastern Cooperative Oncology Group performance status of 0 or 1, 88.7%; and prior regimen of 0-1/≥2, 88.7%/11.3%), 128 non-small-cell lung cancer, 35 gastric cancer, 33 head and neck cancer, 24 melanoma, 19 renal cell carcinoma, 13 urothelial carcinoma, 12 esophageal cancer, 5 malignant mesothelioma of pleura, 2 endometrial cancer, and 4 other cancer were included. The number of patients with positive ANA, Tg, TPO, PA-IgG, GAD, and AchR Abs was 52 (24.9%), 38 (14.5%), 11 (10.1%), 6 (3.5%), 5 (2.0%), and 1 (0.5%), respectively. There was no association between the development of any irAEs and Abs positivity, while thyroid dysfunction developed more frequently among patients with than without Tg Ab or TPO Ab (39.5% versus 12.5%, P < 0.01; 45.5% versus 14.3%, P = 0.02).

Conclusions: The clinical utility of comprehensive measurement of autoimmune disease-related Abs before introduction of ICI therapy was limited for predicting irAE. However, Tg and TPO Abs were risk factors as regards the development of ICI-induced thyroid dysfunction.

Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.

In plain English

This retrospective study reviewed the records of 275 patients with advanced solid tumors at St. Marianna University Hospital in Kawasaki, Japan. Between July 2014 and December 2020, these patients first received immune checkpoint inhibitor drugs: nivolumab, pembrolizumab, atezolizumab, or nivolumab plus ipilimumab. The study did not examine asbestos. Five patients had malignant mesothelioma of pleura, but their results were not reported separately. The authors tested whether six autoimmune disease-related antibodies, measured before treatment, predicted immune-related side effects. Of the 275 patients, 124 (45.1%) had at least one such side effect. Overall, having an antibody was not associated with having an immune-related side effect or with stopping treatment, although some specific side effects differed. Thyroid dysfunction was more frequent in patients with anti-thyroglobulin antibody (39.5% versus 12.5% without) and with anti-thyroid peroxidase antibody (45.5% versus 14.3%). Interstitial pneumonitis was more frequent with anti-GAD antibody (60.0% versus 7.9%), although the authors said this relationship was unclear. The authors concluded that broad antibody testing was of limited use for predicting side effects. They also concluded that the two thyroid antibodies were risk factors for thyroid dysfunction caused by the treatment. They noted small numbers and possible selection bias.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Retrospective single-institution review of medical records
• Who was studied: 275 patients with advanced solid tumors who first received immune checkpoint inhibitor therapy between July 2014 and December 2020 at St. Marianna University Hospital, Kawasaki, Japan. Patients treated in clinical trials were excluded. Median age was 70 years (range 34-91), and 177 (64.4%) were male. Cancers were 128 non-small-cell lung cancer, 35 gastric, 33 head and neck, 24 melanoma, 19 renal cell carcinoma, 13 urothelial carcinoma, 12 esophageal, 5 malignant mesothelioma of pleura, 2 endometrial and 4 other.
• Exposure: Immune checkpoint inhibitor treatment: 193 patients received nivolumab, 67 pembrolizumab, 10 atezolizumab, and 5 nivolumab plus ipilimumab. The factor analyzed was positivity, before treatment, for six antibodies: anti-nuclear antibody (ANA), anti-thyroglobulin (Tg), anti-thyroid peroxidase (TPO), anti-GAD, anti-acetylcholine esterase receptor (AchR), and platelet-associated IgG (PA-IgG). No asbestos exposure was studied.
• Main results:
  • Positive results before treatment, among patients tested for each antibody: ANA 52 (24.9%, of 209), Tg 38 (14.5%, of 262), TPO 11 (10.1%, of 109), PA-IgG 6 (3.5%, of 172), GAD 5 (2.0%, of 247), and AchR 1 (0.5%, of 218). The denominators are taken from Table 4.
  • Of all 275 patients, 124 (45.1%) had any immune-related adverse event. The most common was thyroid dysfunction, in 44 patients (16.0%).
  • Of the 124 patients with immune-related adverse events, 26 (21.0%) discontinued treatment because of them.
  • Antibody positivity before treatment was not associated with the overall outcome of developing an immune-related adverse event, or with discontinuing treatment. Specific events did show associations, which are listed below.
  • Patients positive for PA-IgG antibody tended to have a higher rate of immune-related adverse events than those without it (83.3% versus 43.4%). This difference was not statistically significant (P = 0.09).
  • Thyroid dysfunction occurred in 15 of 38 patients (39.5%) with Tg antibody versus 28 of 224 (12.5%) without it (P less than 0.01). It occurred in 5 of 11 patients (45.5%) with TPO antibody versus 14 of 98 (14.3%) without it (P = 0.02).
  • Interstitial pneumonitis occurred in 3 of 5 patients (60.0%) with GAD antibody versus 19 of 242 (7.9%) without it (P less than 0.01). The authors said the relationship between GAD antibody and interstitial pneumonitis is unclear.
• The authors' conclusion: The authors concluded that comprehensive measurement of autoimmune disease-related antibodies before immune checkpoint inhibitor therapy was of limited use for predicting immune-related adverse events. They also concluded that Tg and TPO antibodies were risk factors for thyroid dysfunction caused by the therapy.
• Limitations the authors state:
  • Antibody positivity and some adverse events, such as type 1 diabetes, were very rare, so the sample was relatively small for the analyses.
  • Because many cancer types were included, the data could not be analyzed by cancer type.
  • There was a risk of selection bias because the definition of an immune-related adverse event was ambiguous.
  • It was unclear whether other antibodies that were not measured, such as islet-cell antibodies, contributed to the adverse events.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer.

Medical terms in this study, explained in our Lexicon: checkpoint inhibitors, Immune-Related Adverse Events, Performance Status, Lung Cancer, Stomach Cancer, Carcinoma, Esophageal Cancer, Mesothelioma.

Related studies

• Registry study of immune-related adverse events using electronic patient-reported outcome in patients with cancer receiving immune checkpoint inhibitors: protocol for a multicentre cohort study — T. Hirata, T. Kawaguchi, et al. (2023)
• Five-year survival and clinical correlates among patients with advanced non-small cell lung cancer, melanoma and renal cell carcinoma treated with immune check-point inhibitors in Australian tertiary oncology centres — L.J. Brown, I.P. da Silva, et al. (2023)
• Pre-treatment soluble PD-L1 as a predictor of overall survival for immune checkpoint inhibitor therapy: a systematic review and meta-analysis — Á. Széles, T. Fazekas, et al. (2023)
• The efficacy of immune checkpoint inhibitors in thoracic malignancies — J. Remon, F. Facchinetti, et al. (2021)
• Potential of fluoropyrimidine to be an immunologically optimal partner of immune checkpoint inhibitors through inducing immunogenic cell death for thoracic malignancies — H. Kozai, H. Ogino, et al. (2024)
• LAG3 is an independent prognostic biomarker and potential target for immune checkpoint inhibitors in malignant pleural mesothelioma: a retrospective study — K. Arimura, K. Hiroshima, et al. (2023)

Browse more research in ESMO Open, or return to medical research.