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

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.This article has supplementary material available from

Immune checkpoint inhibitor-associated interstitial lung diseases: some progress but still many issues

“…Indeed, this series represent the largest series of well-defined ICI-ILDs with a systematic assessment of clinical and radiological findings [3]. The estimate of overall incidence was 3.5%, which is consistent with recent meta-analyses [2,4].…”

“…Indeed, the term "pneumonitis", usually used for lung immune-related adverse events, covers a wide and overlapping spectrum of pulmonary manifestations. In this context, the study by DELAUNAY et al[3] brings major additional information to this field regarding the presentation, management and evolution of what are referred to as ICI-associated interstitial lung diseases (ILDs).Indeed, this series represent the largest series of well-defined ICI-ILDs with a systematic assessment of clinical and radiological findings [3]. The estimate of overall incidence was 3.5%, which is consistent with…”

“…an ICI). In this study, a significant proportion of patients underwent bronchoalveolar lavage (>50%), allowing the authors to confirm its potential role in the diagnosis of ICI-ILD since T-lymphocytic alveolitis was found in 80% of cases [3]. Even if the mechanisms of ICI-ILD are not clearly demonstrated, these results infer a deregulation of T-cells as supported by pathological assessments showing evidence of inflammation and lymphocytic infiltration [3].…”

“…Disturbingly, ICI-ILD is also characterised by a very wide range of clinical and radiological presentations. The most common pattern was organising pneumonia but this represented only a quarter of cases, followed by hypersensitivity pneumonitis, nonspecific interstitial pneumonia and bronchiolitis [3]. Notably, it was not possible to describe a suggestive pattern in a third of the patients.…”

“…Indeed, the term "pneumonitis", usually used for lung immune-related adverse events, covers a wide and overlapping spectrum of pulmonary manifestations. In this context, the study by DELAUNAY et al [3] brings major additional information to this field regarding the presentation, management and evolution of what are referred to as ICI-associated interstitial lung diseases (ILDs).…”