Karen Bitton1, Jean-Marie Michot2, Emmanuel Barreau3, Olivier Lambotte4, Oscar Haigh5, Aurélien Marabelle6, Anne-Laure Voisin7, Christine Mateus8, Anne-Laure Rémond9, Chloé Couret10, Stéphane Champiat2, Marc Labetoulle11, Antoine Rousseau12. 1. Service d'Ophtalmologie, DHU Vision & Handicaps, Centre de référence pour les maladies rares en ophtalmologie (OPHTARA), Hôpital Bicêtre, Assistance Publique Hôpitaux de Paris, Le Kremlin-Bicêtre, France; Université Paris-Sud, Le Kremlin-Bicêtre, France. 2. Département d'Innovation Thérapeutique et d'Essais Précoces, Université Paris-Saclay, Gustave Roussy, Villejuif, France. 3. Service d'Ophtalmologie, DHU Vision & Handicaps, Centre de référence pour les maladies rares en ophtalmologie (OPHTARA), Hôpital Bicêtre, Assistance Publique Hôpitaux de Paris, Le Kremlin-Bicêtre, France. 4. Service de Médecine Interne et Immunologie Clinique, Hôpital Bicêtre, Assistance Publique Hôpitaux de Paris, Le Kremlin-Bicêtre, France; Université Paris-Sud, Le Kremlin-Bicêtre, France; Immunology of Viral Infections and Autoimmune Diseases, INSERM U1184, Le Kremlin-Bicêtre, France; Department of Immunology of Viral and Auto-immune Disease, UMR1184, CEA, CEA, DSV/iMETI, IDMIT, Fontenay-aux-Roses, France. 5. Department of Immunology of Viral and Auto-immune Disease, UMR1184, CEA, CEA, DSV/iMETI, IDMIT, Fontenay-aux-Roses, France. 6. Département d'Innovation Thérapeutique et d'Essais Précoces, Université Paris-Saclay, Gustave Roussy, Villejuif, France; INSERM U1015, Gustave Roussy, Villejuif, France. 7. Unité Fonctionnelle de Pharmacovigilance, Université Paris-Saclay, Gustave Roussy, Villejuif, France. 8. Department of Supportive Care, Université Paris-Saclay, Gustave Roussy, Villejuif, France. 9. Service d'Ophtalmologie, DHU Vision & Handicaps, Centre de référence pour les maladies rares en ophtalmologie (OPHTARA), Hôpital Pitié-Salpétrière, Assistance Publique Hôpitaux de Paris, Paris, France. 10. Service d'Ophtalmologie, CHU de Nantes, Nantes, France. 11. Service d'Ophtalmologie, DHU Vision & Handicaps, Centre de référence pour les maladies rares en ophtalmologie (OPHTARA), Hôpital Bicêtre, Assistance Publique Hôpitaux de Paris, Le Kremlin-Bicêtre, France; Université Paris-Sud, Le Kremlin-Bicêtre, France; Immunology of Viral Infections and Autoimmune Diseases, INSERM U1184, Le Kremlin-Bicêtre, France; Department of Immunology of Viral and Auto-immune Disease, UMR1184, CEA, CEA, DSV/iMETI, IDMIT, Fontenay-aux-Roses, France. 12. Service d'Ophtalmologie, DHU Vision & Handicaps, Centre de référence pour les maladies rares en ophtalmologie (OPHTARA), Hôpital Bicêtre, Assistance Publique Hôpitaux de Paris, Le Kremlin-Bicêtre, France; Université Paris-Sud, Le Kremlin-Bicêtre, France; Immunology of Viral Infections and Autoimmune Diseases, INSERM U1184, Le Kremlin-Bicêtre, France; Department of Immunology of Viral and Auto-immune Disease, UMR1184, CEA, CEA, DSV/iMETI, IDMIT, Fontenay-aux-Roses, France. Electronic address: antoine.rousseau@aphp.fr.
Abstract
PURPOSE: Immune checkpoint inhibitors (ICI) targeting the programmed cell death protein 1 (PD-1), or its ligand PD-L1, are the mainstay of metastatic cancer treatment. Patients receiving these treatments may develop immune-related adverse events (irAEs). This study aimed to estimate the prevalence and describe the clinical patterns of moderate-to-severe ocular irAEs-associated with anti-PD-(L)1 treatment. DESIGN: Prospective case series. METHODS: This study included patients recruited via (1) a single-center prospective cohort and (2) a national pharmacovigilance registry between June 2014 and March 2018, and focused on patients with moderate-to-severe ocular irAEs following anti-PD-(L)1. All patients underwent a comprehensive ophthalmologic assessment. The main outcome measure was the prevalence of moderate-to-severe ocular irAEs. RESULTS: Of a total of 745 patients included in the prospective cohort, 3 developed moderate-to-severe ocular irAEs, providing a prevalence of 0.4% and an incidence of 0.7 per 1000 patient-months of treatment. An additional 5 cases of moderate-to-severe ocular irAEs were reported through the national registry. From these 8 patients, 5 presented with intraocular inflammation, 2 with ocular surface disease, and 1 with orbital myopathy. Five patients (62.5%) experienced additional extraophthalmologic irAEs. Ocular irAEs led to permanent discontinuation of anti-PD-(L)1 in 4 patients. Treatment by local and/or systemic corticosteroids allowed resolution or control of the ocular symptoms in 7 of 8 patients. CONCLUSION: Although uncommon, anti-PD-(L)1-associated ocular complications may be sight-threatening and lead to discontinuation of anti-PD-(L)1 treatments. Patients complaining of eye problems while receiving ICI treatment should immediately be seen by an ophthalmologist.
PURPOSE: Immune checkpoint inhibitors (ICI) targeting the programmed cell death protein 1 (PD-1), or its ligand PD-L1, are the mainstay of metastatic cancer treatment. Patients receiving these treatments may develop immune-related adverse events (irAEs). This study aimed to estimate the prevalence and describe the clinical patterns of moderate-to-severe ocular irAEs-associated with anti-PD-(L)1 treatment. DESIGN: Prospective case series. METHODS: This study included patients recruited via (1) a single-center prospective cohort and (2) a national pharmacovigilance registry between June 2014 and March 2018, and focused on patients with moderate-to-severe ocular irAEs following anti-PD-(L)1. All patients underwent a comprehensive ophthalmologic assessment. The main outcome measure was the prevalence of moderate-to-severe ocular irAEs. RESULTS: Of a total of 745 patients included in the prospective cohort, 3 developed moderate-to-severe ocular irAEs, providing a prevalence of 0.4% and an incidence of 0.7 per 1000 patient-months of treatment. An additional 5 cases of moderate-to-severe ocular irAEs were reported through the national registry. From these 8 patients, 5 presented with intraocular inflammation, 2 with ocular surface disease, and 1 with orbital myopathy. Five patients (62.5%) experienced additional extraophthalmologic irAEs. Ocular irAEs led to permanent discontinuation of anti-PD-(L)1 in 4 patients. Treatment by local and/or systemic corticosteroids allowed resolution or control of the ocular symptoms in 7 of 8 patients. CONCLUSION: Although uncommon, anti-PD-(L)1-associated ocular complications may be sight-threatening and lead to discontinuation of anti-PD-(L)1 treatments. Patients complaining of eye problems while receiving ICI treatment should immediately be seen by an ophthalmologist.
Authors: LeAnne Young; Shanda Finnigan; Howard Streicher; Helen X Chen; James Murray; H Nida Sen; Elad Sharon Journal: J Immunother Cancer Date: 2021-07 Impact factor: 13.751