Ocular side effects of checkpoint inhibitors

Alba‐Linero, Carmen; Alba, Emilio

doi:10.1016/j.survophthal.2021.01.001

Cited by 17 publications

(16 citation statements)

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“…Although ocular irAEs are infrequent based on the previous study, they can cause a deterioration of the quality of life and exert an influence on the compliance of patients. Lots of studies have reported the ocular adverse events secondary to ICIs (19,25,26,30,31,153,(164)(165)(166)(167)(168) and the grade of the adverse events had been published recently based on Common Terminology Criteria for Adverse Events. While no study had reported the ocular irAEs in lung cancer.…”

Section: Discussionmentioning

confidence: 99%

Ocular Immune-Related Adverse Events Associated With Immune Checkpoint Inhibitors in Lung Cancer

Zhou

Wei

2021

Front. Immunol.

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Immune checkpoint inhibitors (ICIs) are novel immunotherapy-based drugs that have become increasingly popular in the treatment of lung cancer. Researchers have recognized ocular immune-related adverse events (irAEs) secondary to ICIs because of their vision-threatening characteristics. However, they are incompletely characterized and no studies have reported the ICI-related ocular irAEs in lung cancer. Therefore, we aimed to comprehensively illustrate the clinical characteristics, contributory factors, diagnosis, and management of ICI-related ocular irAEs in lung cancer, based on previously reported 79 patients. Ophthalmoplegia (40.51%), uveitis (20.25%), and dry eye (17.72%) were the most common ICI-related ocular irAEs in lung cancer. Ptosis was the most common (36.71%) and the highest mortality (23.33%) of ophthalmoplegia. Patients in Asia and patients who underwent combination therapy with programmed cell death-1 and cytotoxic T-lymphocyte-associated antigen 4 inhibitors demonstrated significantly higher frequency of ophthalmoplegia than other ocular irAEs. Most ICI-related ophthalmoplegia and uveitis in lung cancer were observed in the first 10 weeks following the initiation of ICIs. Furthermore, the onset time of dry eye and other ocular irAEs was much longer. In addition, 92.31% of the patients with ocular irAEs other than ophthalmoplegia could be remised. In conclusion, ocular irAEs secondary to ICIs in lung cancer are non-negligible, particularly ophthalmoplegia. Ethnicity and the type of ICIs play important roles in the distribution of ocular irAEs. ICI-related ophthalmoplegia in lung cancer presented with early onset and worse prognosis features, thus necessitating further attention.

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Section: Discussionmentioning

confidence: 99%

Ocular Immune-Related Adverse Events Associated With Immune Checkpoint Inhibitors in Lung Cancer

Zhou

Wei

2021

Front. Immunol.

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“…Eine breite Anwendung von ICI in den letzten Jahren hat seither zu einer Häufung von Berichten über deren Nebenwirkungen an verschiedenen Organsystemen, u. a. auch am Auge, geführt [8]. Die Inzidenz und Bedeutung okulärer Nebenwirkungen infolge einer Therapie mit ICI wurde anfangs unterschätzt, da diese zur Zeit der Durchführung der klinischen Wirksamkeitsstudien noch nicht bekannt waren [22].…”

Section: Klassenspezifische Nebenwirkungen Von Checkpoint-inhibitoren...unclassified

“…Die häufigste klinische Manifestation einer Nebenwirkung unter ICI ist ein schweres Sicca-Syndrom, das in bis zu 24 % beobachtet wurde [22,32]. Etwa [12,32,33].…”

Section: Spektrum Und Inzidenz Okulärer Nebenwirkungen Unter Immun-ch...unclassified

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Uveitisinduktion durch immunonkologische Therapien, speziell Checkpoint-Inhibitoren

Garweg

2022

Klin Monbl Augenheilkd

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Zusammenfassung Hintergrund Immun-Checkpoint- und BRAF-/MEK-Inhibitoren (ICI) haben eine zentrale Stellung in der Krebstherapie eingenommen, da sie eine erhebliche Lebensverlängerung bei einer guten Verträglichkeit und Lebensqualität bewirken. Sie sind jedoch mit stoffklassenspezifischen, nicht toxischen immunologischen Nebenwirkungen, darunter auch Entstehung einer Uveitis, behaftet. In dieser Übersicht soll der aktuelle Kenntnisstand zu Wirkprinzip und systemischen und okulären Nebenwirkungen der ICI dargestellt werden. Methoden Dieser Übersicht liegt eine Literatursuche in PubMed, der Datenbank des National Institute of Health der USA (https://www.ncbi.nlm.nih.gov/pubmed) mit den Stichworten „uveitis“ AND „drug-induced“ AND/OR „immune checkpoint inhibitor“ zugrunde. Alle relevant erscheinenden Publikationen der letzten 5 Jahre wurden zusammen mit den darin zitierten Querverweisen ausgewertet. Ergebnisse Ein klassenspezifisches Phänomen der sonst gut verträglichen ICI ist ihre Fähigkeit, eine systemische und okuläre Autoimmunität auszulösen. Diese unterscheidet sich von toxischen Nebenwirkungen durch ihre Dosisunabhängigkeit. Okuläre Nebenwirkungen treten bei 3% der Patienten auf, wobei ein Melanom als Grunderkrankung und eine Therapie mit Pembrolizumab das Risiko um ein Mehrfaches erhöhen. Eine frühe Diagnose und systemische Steroidtherapie dieser potenziell lebensbedrohlichen Nebenwirkung erlauben in > 90% die Erhaltung der Sehfunktion und Lebensqualität, ohne die ICI-Therapie abzusetzen. Schlussfolgerung Das therapeutische Ansprechen von Malignomen auf ICI bezüglich des Überlebens und der Verträglichkeit, insbesondere bei Melanomen, lässt eine zunehmende Anwendung von ICI auch in Therapiekombinationen und damit eine Zunahme der immunologischen Komplikationen im klinischen Alltag erwarten. In Anbetracht einer Mortalität von unbehandelt bis zu 3% infolge immunvermittelter Nebenwirkungen an multiplen Organen ist eine rasche interdisziplinäre Abklärung und rechtzeitige aggressive Behandlung zwingend, führt aber meist auch zu erfreulichen funktionellen Ergebnissen.

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“…Although ICIs display proven anticancer efficacy, the enhanced immune response that occurs during treatment with these drugs may elicit immune-related adverse events (irAEs) in various body systems and organs [ 2 – 16 ]. Some irAEs are associated with improved overall survival or progression-free survival, and are hence regarded as a marker for the anticancer efficacy of some ICIs [ 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

Validation of an online application to identify potential immune-related adverse events associated with immune checkpoint inhibitors based on the patient’s symptoms

et al. 2022

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Background Immune checkpoint inhibitors (ICIs) are increasingly being used to treat malignancies. Some patients experience immune-related adverse events (irAEs), which may affect any organ/tissue. IrAEs are occasionally fatal and usually have nonspecific symptoms. We developed a three-step application (https://irae-search.com/) to provide healthcare professionals with information on the diagnosis, treatment options, and published reports for 38 categories of irAEs encountered in clinical practice. Methods IrAEs reported in ≥5 cases were identified from articles published between October 2018 and August 2020 by searching Japanese (SELIMIC, JAPIC-Q Service, and JMED Plus) and international (MEDLINE, EMBASE, Derwent Drug File) databases. The cases’ symptoms were entered into the application to identify irAEs, which were verified using the reported diagnosis, to evaluate the application’s sensitivity and specificity. Results Overall, 1209 cases (1067 reports) were analyzed. The three most common categories of irAEs were pituitary or adrenal disorders (14% of cases), skin disorders (13%), and diabetes mellitus (10%). The top three primary diseases were lung cancer (364 cases), melanoma (286 cases), and renal cell carcinoma (218 cases). The average sensitivity was 90.8% (range 44.4%–100.0%) initially, and improved to 94.8% (range 83.3%–100.0%) after incorporating the symptoms reported in published cases into the application’s logic for two irAE categories. The average specificity was 79.3% (range 59.1% [thyroid disorders]–98.2% [arthritis]). Conclusion irAE Search is an easy-to-use application designed to help healthcare professionals identify potential irAEs in ICI-treated patients in a timely manner to facilitate prompt management/treatment. The application showed high sensitivity and moderate-to-high specificity for detecting irAEs.

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Ocular side effects of checkpoint inhibitors

Cited by 17 publications

References 100 publications

Ocular Immune-Related Adverse Events Associated With Immune Checkpoint Inhibitors in Lung Cancer

Ocular Immune-Related Adverse Events Associated With Immune Checkpoint Inhibitors in Lung Cancer

Uveitisinduktion durch immunonkologische Therapien, speziell Checkpoint-Inhibitoren

Validation of an online application to identify potential immune-related adverse events associated with immune checkpoint inhibitors based on the patient’s symptoms

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