Chronic Pneumonitis in Patients with NSCLC Treated with Immune Checkpoint Inhibitor Therapy

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The recent development of immune checkpoint inhibitors (ICIs) has advanced the treatment of non–small-cell lung cancer (NSCLC), which is promising news as the prognosis for advanced NSCLC is poor and standard treatment has limited effect.1 Up to 10% of patients with NSCLC treated with ICIs experience pneumonitis, a rare but potentially fatal adverse effect.2 While most pneumonitis cases respond to the recommended 4 to 6 weeks of treatment with corticosteroids, a small percentage will develop recurrent pneumonitis when ICI therapy resumes.2 In a few cases, patients will develop chronic or relapsing ICI pneumonitis despite discontinuation of ICI treatment and corticosteroid treatment lasting ≥12 weeks.2,3

This complication was evaluated in a study presented at the 2021 American Society of Clinical Oncology annual meeting. Researchers investigated the clinical features and courses experienced by 869 patients with NSCLC treated with ICIs between 2011 and 2019 who developed chronic pneumonitis.3 The patients were evaluated with chest computed tomography (CT) scans to classify the lung imaging patterns.3 Pneumonitis requiring treatment with steroids for a total of ≥12 weeks, either continuously or for multiple time periods, was defined as chronic pneumonitis.3 If the initial course of steroid treatment was given continuously for ≥12 weeks with no interruption, the pneumonitis was classified as primary refractory pneumonitis.3 Recurrent pneumonitis was defined as a subsequent pneumonitis episode from ICI rechallenge, and pneumonitis flare was defined as an episode of pneumonitis after steroids were tapered without an ICI rechallenge.3

ICI pneumonitis developed in 44 patients and 50% of these patients experienced chronic pneumonitis requiring a median of 25.9 total weeks of corticosteroid therapy.3 Additional immunosuppressant therapy was necessary for 4 patients.3 The most common CT pattern found in all pneumonitis cases (30 of 44) was cryptogenic organizing pneumonia (COP).3 COP was also found in 14 of 22 patients with chronic pneumonitis.3 Primary refractory pneumonitis affected 14 of the 22 patients with chronic pneumonitis.3 The remaining 8 patients were weaned off of steroids within 12 weeks, but they developed episode(s) of pneumonitis that resulted in ≥12 weeks of steroid therapy in total.3 Patients with primary refractory pneumonitis had an average of 1.8 months to pneumonitis development, whereas the 8 patients experiencing recurrent pneumonitis had an average of 5.5 months to pneumonitis development.3

ICI treatment was permanently discontinued in 17 of the 22 patients and 9 of the 17 experienced pneumonitis flare after their steroid doses were tapered.3 This made it necessary for them to receive additional steroid doses, some repeatedly.3 When 5 of the 22 patients were rechallenged with ICIs, 4 had recurrent pneumonitis.3

References

  1. Onoi K, Chihara Y, Uchino J, et al. Immune checkpoint inhibitors for lung cancer treatment: a review. J Clin Med. 2020;9:1362.
  2. Naidoo J, Cottrell TR, Lipson EJ, et al. Chronic immune checkpoint inhibitor pneumonitis [published correction appears in J Immunother Cancer. 2020 Nov;8(2):]. J Immunother Cancer. 2020;8:e000840.
  3. Stuart J, Ricciuti B, Machado Alessi J, et al. Chronic immune checkpoint inhibitor (ICI) pneumonitis in patients (pts) with non-small cell lung cancer (NSCLC). J Clin Oncol. 2021;39(15_suppl):9103-9103.

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