Immune-checkpoint inhibitors associated with interstitial lung disease in cancer patients

Myriam Delaunay 1 Jacques Cadranel 2, 3, 4 Amélie Lusque 5 Nicolas Meyer 6 Valérie Gounaut 7 Denis Moro-Sibilot 8 Jean-Marie Michot 9, 10 Judith Raimbourg 11, 12 Nicolas Girard 13 Florian Guisier 14, 15 David Planchard Anne-Cécile Metivier 16 Pascale Tomasini 17 Eric Dansin 18 Maurice Pérol 19 Marion Campana 20 Oliver Gautschi 21 Martin Früh 22 Jean-David Fumet 23 Clarisse Audigier-Valette 24 Sébastien Couraud 25, 26 Stéphane Dalle 27, 28 Marie-Thérèse Leccia 29 Marion Jaffro 30 Samia Collot 30 Gregoire Prevot 1 Julie Milia 1 Julien Mazières 1, *
* Corresponding author
1 Service de pneumologie [Toulouse]
2 Service de pneumologie et réanimation [CHU Tenon]
3 Sorbonne Universités
4 UPMC - Université Pierre et Marie Curie - Paris 6
5 Bureau des Essais Cliniques - Cellule Biostatistique [IUCT Oncopole, Toulouse]
6 Département de Dermatologie [IUCT Oncopole, Toulouse]
7 Service d’oncologie thoracique et essais précoces [CHU Bichat]
8 Département d'oncologie thoracique [CHU Grenoble]
9 Département d'hématologie [Gustave Roussy]
10 DITEP - Département d’Innovation Thérapeutique et essais précoces [Gustave Roussy]
11 Département d'oncologie médicale [Saint Herblain]
12 CRCNA / Equipe 9 - Apoptose et Progression tumorale
INSERM - Institut National de la Santé et de la Recherche Médicale : U892, IRS-UN - Institut de Recherche en Santé de l'Université de Nantes
13 Service de pneumologie [Centre Hospitalier Lyon Sud - HCL]
14 Service de pneumologie, oncologie thoracique et soins intensifs respiratoires [Rouen]
15 CIC Rouen - Centre d'Investigation Clinique [Rouen]
16 Service de Pneumologie [Suresne]
17 Service d'oncologie multidisciplinaire innovations thérapeutiques [Hôpital Nord - APHM]
18 Département de Cancérologie Générale [Lille]
19 Département de Cancérologie Médicale [Lyon]
20 Service de Pneumologie [CHRU Tours]
21 Medical Oncology Department [Luzern, Switzerland]
22 Medical Oncology Department [St Gallen, Switzerland]
23 Département d'oncologie médicale [Centre Georges-François Leclerc]
24 Service de Pneumonologie [Toulon]
25 Service de Pneumologie Aiguë Spécialisée et Cancérologie Thoracique [HCL Lyon]
26 EA3738 - Ciblage thérapeutique en Oncologie
27 Service de Dermatologie [HCL, Lyon]
28 CRCL - Centre de Recherche en Cancérologie de Lyon
29 Service de Dermatologie [CHU de Grenoble site Nord]
30 Service de Radiologie [CHU Toulouse]
Abstract : Immunotherapy is becoming a standard of care for many cancers. Immune-checkpoint inhibitors (ICI) can generate immune-related adverse events. Interstitial lung disease (ILD) has been identified as a rare but potentially severe event.Between December 2015 and April 2016, we conducted a retrospective study in centres experienced in ICI use. We report the main features of ICI-ILD with a focus on clinical presentation, radiological patterns and therapeutic strategies.We identified 64 (3.5%) out of 1826 cancer patients with ICI-ILD. Patients mainly received programmed cell death-1 inhibitors. ILD usually occurred in males, and former or current smokers, with a median age of 59 years. We observed 65.6% grade 2/3 severity, 9.4% grade 4 severity and 9.4% fatal ILD. The median (range) time from initiation of immunotherapy to ILD was 2.3 (0.2-27.4) months. Onset tended to occur earlier in lung cancer versus melanoma: median 2.1 and 5.2 months, respectively (p=0.02). Ground-glass opacities (81.3%) were the predominant lesions, followed by consolidations (53.1%). Organising pneumonia (23.4%) and hypersensitivity pneumonitis (15.6%) were the most common patterns. Overall survival at 6 months was 58.1% (95% CI 37.7-73.8%).ICI-ILD often occurs early and displays suggestive radiological features. As there is no clearly identified risk factor, oncologists need to diagnose and adequately treat this adverse event.
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HCL | ICR | UPMC | CHLS | CGFL | LAMBRET | ICO | GAUDUCHEAU | FNCLCC | CRCNA | UNIV-LYON1 | COMUE-NORMANDIE | UNIV-NANTES | UNIROUEN | IGR | UNIV-PARIS-SACLAY | SORBONNE-UNIVERSITE | CRCL | UNIV-TLSE3

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Myriam Delaunay, Jacques Cadranel, Amélie Lusque, Nicolas Meyer, Valérie Gounaut, et al.. Immune-checkpoint inhibitors associated with interstitial lung disease in cancer patients. European Respiratory Journal, European Respiratory Society, 2017, 50 (5), ⟨10.1183/13993003.00050-2017⟩. ⟨inserm-01819272⟩

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