Prognostic significance of the radiologic features of pneumonitis induced by anti‐PD‐1 therapy

Watanabe, Satoshi; Ota, Takayo; Hayashi, Masachika; Ishikawa, Hiroyuki; Otsubo, Aya; Shoji, Shuichi; Nozaki, Kohei; Ichikawa, Kosuke; Kondo, Rie; Miyabayashi, Takao; Miura, Satoru; Tanaka, Hiroshi; Abe, Tetsuya; Okajima, Masaaki; Tomita, Masaki; Ishida, Takashi; Iwashima, Akira; Sato, Kazuhiro; Yoshizawa, Hirohisa; Kikuchi, Toshiaki

doi:10.1002/cam4.2974

Cited by 17 publications

(8 citation statements)

References 22 publications

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“…The dispersion of our data may be due to the different patterns of interstitial lung toxicity observed in our relatively small cohort. The main radiological patterns were OP, HP-like parenchymal features and GGO, in line with previous data [ 8 , 27 , 28 ]; however, other radiological interstitial features were observed in these patients, including NSIP and UIP patterns. In our study, fibrotic ILD developed in a small percentage of patients, with a longer, albeit not significant, latency with respect to GGO and HP-like parenchymal features.…”

Section: Discussionsupporting

confidence: 91%

“…Concerning the prognostic significance of different CT patterns, to our knowledge, only a paper by Watanabe et al [ 28 ] reported a direct comparison, demonstrating that patients developing GGO were affected by a worse prognosis and life expectancy than in those with OP. Our data seem to be in line with these observations, as the majority of patients who died early showed chest HRCT evidence of the GGO pattern.…”

Section: Discussionmentioning

confidence: 99%

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Immune-Checkpoint-Inhibitor-Related Lung Toxicity: A Multicentre Real-Life Retrospective Portrait from Six Italian Centres

Cameli

Faverio

Ferrari

et al. 2022

Life

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Background: Immune checkpoint inhibitors (ICIs) have revolutionized the therapeutic horizons of various cancers. However, immune-related adverse events have been reported, including interstitial lung diseases. Our aim was to describe the clinical and radiological features and survival of a multicentre cohort of patients who developed ICI-related lung toxicity. Methods: Six Italian centres were involved in the study. Patients who were treated with anti-PD-1/PD-L1 and CTLA-4 mAbs and developed ICI-related lung toxicity were recruited retrospectively to study clinical, radiological, immunological and survival data. Results: A total of 41 patients (25 males, 66.8 ± 9.9 years) were enrolled. Lung toxicity occurred after 204.3 ± 208.3 days of therapy, with ground glass opacities being the most common HRCT pattern (23 cases). Male sex, lung cancer and acute respiratory failure were associated with a shorter latency of toxicity (p = 0.0030, p = 0.0245 and p = 0.0390, respectively). Patients who required high-flow oxygen therapy showed significantly worse survival (p = 0.0028). Conclusions: Our cohort showed heterogeneous clinical and radiological aspects of ICI-related lung toxicity, with a latency not limited to the first year of treatment. Severity was mainly mild to moderate, although life-threatening events did occur. Our data indicate that strict long-term follow-up is needed to enable early diagnosis and appropriate management.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Immune-Checkpoint-Inhibitor-Related Lung Toxicity: A Multicentre Real-Life Retrospective Portrait from Six Italian Centres

Cameli

Faverio

Ferrari

et al. 2022

Life

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“…Specific findings on chest CT include traction bronchiectasis, consolidation, reticular opacities, ground glass opacities (GGOs), centrilobular nodularity, and honeycombing, of which GGOs are present in the majority of patients ( 66 ). In addition, GGO was indicated as a significant predictor of worse overall survival ( 67 ). Clinically, the situation will be more complicated, and mixed patterns may be observed.…”

Section: Occurrence Of Cip During Pd-1/pd-l1 Blockadementioning

confidence: 99%

“…In addition, they also observed increased numbers of central memory T cells and decreased expression of CTLA-4 and PD-1 in regulatory T cells (Tregs). Enriched IFNg + IL-17-CD8 + T and CXCR3 + CCR6 + Th17/Th1 cells were observed in the BALF of CIP compared with infection pneumonia in acute myeloid leukemia and myelodysplastic syndrome ( 67 ).…”

Section: Occurrence Of Cip During Pd-1/pd-l1 Blockadementioning

confidence: 99%

Checkpoint Inhibitor Pneumonitis Induced by Anti-PD-1/PD-L1 Therapy in Non-Small-Cell Lung Cancer: Occurrence and Mechanism

Yin

Yang

et al. 2022

Front. Immunol.

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Immune checkpointty inhibitors (ICIs), particularly those targeting programmed death 1 (PD-1) and anti-programmed death ligand 1 (PD-L1), enhance the antitumor effect by restoring the function of the inhibited effector T cells and produce durable responses in a large variety of metastatic and late patients with non-small-cell lung cancer. Although often well tolerated, the activation of the immune system results in side effects known as immune-related adverse events (irAEs), which can affect multiple organ systems, including the lungs. The occurrence of severe pulmonary irAEs, especially checkpoint inhibitor pneumonitis (CIP), is rare but has extremely high mortality and often overlaps with the respiratory symptoms and imaging of primary tumors. The development of CIP may be accompanied by radiation pneumonia and infectious pneumonia, leading to the simultaneous occurrence of a mixture of several types of inflammation in the lungs. However, there is a lack of authoritative diagnosis, grading criteria and clarified mechanisms of CIP. In this article, we review the incidence and median time to onset of CIP in patients with non-small-cell lung cancer treated with PD-1/PD-L1 blockade in clinical studies. We also summarize the clinical features, potential mechanisms, management and predictive biomarkers of CIP caused by PD-1/PD-L1 blockade in non-small-cell lung cancer treatment.

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“…The decision of whether to continue or discontinue ICIs after the occurrence of irAEs is generally based on the type of irAE and its severity (7). We previously reported that ICI-related interstitial lung disease (ILD), whose appearance was ground-glass opacities (GGOs), was a significant predictor of poor survival outcomes (8). However, recent evidence has demonstrated that the occurrence of irAEs is associated with better survival outcomes in patients with NSCLC (9)(10)(11)(12)(13).…”

Section: Introductionmentioning

confidence: 99%

The Prognostic Significance of the Continuous Administration of Anti-PD-1 Antibody via Continuation or Rechallenge After the Occurrence of Immune-Related Adverse Events

et al. 2021

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ObjectivesAlthough immune checkpoint inhibitors (ICIs) have been shown to improve overall survival (OS) in advanced non-small-cell lung cancer (NSCLC) patients, ICIs sometimes cause various types of immune-related adverse events (irAEs), which lead to the interruption of ICI treatment. This study aims to evaluate the clinical significance of the continuation of ICIs in NSCLC patients with irAEs and to assess the safety and efficacy of the readministration of ICIs after their discontinuation due to irAEs.MethodsWe retrospectively identified patients with advanced NSCLC who were treated with first- to third-line anti-programmed cell death-1 (PD-1) therapy from January 2016 through October 2017 at multiple institutions belonging to the Niigata Lung Cancer Treatment Group. Progression-free survival (PFS) and OS from the initiation of ICI treatment were analyzed in patients with and without irAEs, with and without ICI interruption, and with and without ICI readministration. A 6-week landmark analysis of PFS and OS was performed to minimize the lead-time bias associated with time-dependent factors.ResultsOf 231 patients who received anti-PD-1 antibodies, 93 patients (40%) developed irAEs. Of 84 eligible patients with irAEs, 32 patients (14%) continued ICIs, and OS was significantly longer in patients who continued ICIs than that in patients who discontinued ICIs [not reached (95% CI: NE-NE) vs. not reached (95% CI: 22.4–NE); p = 0.025]. Of 52 patients who discontinued ICIs, 14 patients (6.1%) readministered ICIs, and OS in patients with ICI readministration was significantly longer than that in patients without ICI readministration [not reached (95% CI: NE-NE) vs. not reached (95% CI: 8.4–NE); p = 0.031].ConclusionThe current study demonstrated that both the continuation and readministration of ICIs after irAE occurrence improved OS compared to the permanent interruption of ICIs in NSCLC patients with ICI-related irAEs.

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Prognostic significance of the radiologic features of pneumonitis induced by anti‐PD‐1 therapy

Cited by 17 publications

References 22 publications

Immune-Checkpoint-Inhibitor-Related Lung Toxicity: A Multicentre Real-Life Retrospective Portrait from Six Italian Centres

Immune-Checkpoint-Inhibitor-Related Lung Toxicity: A Multicentre Real-Life Retrospective Portrait from Six Italian Centres

Checkpoint Inhibitor Pneumonitis Induced by Anti-PD-1/PD-L1 Therapy in Non-Small-Cell Lung Cancer: Occurrence and Mechanism

The Prognostic Significance of the Continuous Administration of Anti-PD-1 Antibody via Continuation or Rechallenge After the Occurrence of Immune-Related Adverse Events

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