High mortality and poor treatment efficacy of immune checkpoint inhibitors in patients with severe grade checkpoint inhibitor pneumonitis in non‐small cell lung cancer

Abstract

Background The treatment efficacy of immune checkpoint inhibitor (ICI) and clinical outcomes in patients with non‐small cell lung cancer (NSCLC) who develop severe grade checkpoint inhibitor pneumonitis (CIP) are unclear. Here, we report on the treatment efficacy of ICI and prognosis in NSCLC patients with severe grade CIP. Methods In this retrospective cohort study, CIP severity, CIP‐related mortality, and ICI efficacy in 71 patients with advanced NSCLC treated with ICIs were evaluated. Data was obtained from the patients’ medical charts. Results All grade and severe grade CIP were observed in 22 and 11 patients, respectively. The CIP‐related mortality rate was 22.7% (N = 5). An Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of ≥2 and pre‐existing interstitial lung disease (ILD) were significantly associated with the development of severe grade CIP (P = 0.001 and P = 0.035, respectively). The median progression‐free survival (PFS) and overall survival (OS) were significantly shorter in patients with severe grade CIP than in those without severe grade CIP (PFS 1.0 month, 95% confidence interval [CI] 0.5–2.0 vs. 3.5 months, 95% CI 2.0–5.0 months, P = 0.003; OS 3.0 months, 95% CI 0.5–13 vs. 12.7 months, 95% CI 8.0–21.0 months, P = 0.011). Conclusion CIP is a serious complication with a poor prognosis associated with high mortality. The efficacy of ICI is significantly worse in patients with severe grade CIP than in those without severe grade CIP. Whether ICIs should be administered to patients with CIP risk factors, such as an ECOG PS score of ≥2 or pre‐existing ILD, should be carefully assessed.

Outcome and risk factor of immune‐related adverse events and pneumonitis in patients with advanced or postoperative recurrent non‐small cell lung cancer treated with immune checkpoint inhibitors

“…Although several clinical trials revealed that 2.5% to 5% of patients developed ICI pneumonitis, 14 its incidence was higher in the clinical setting than in the clinical trials, and 5.4% to 16.9% of patients experienced ICI pneumonitis 10,11,30 . Tone et al 31 . reported that patients with ICI pneumonitis of grade 3 or higher were associated with shorter median OS than those with ICI pneumonitis of grade 2 or lower or no ICI pneumonitis.…”

The mechanism and risk factors for immune checkpoint inhibitor pneumonitis in non-small cell lung cancer patients

“…Notably, the results regarding this topic were all from retrospective analyses, which were inevitably influenced by bias even after statistical adjustment. Therefore, this issue still needs evaluation in prospective and large sample studies 100 – 102 . Third, the morbidity and mortality of CIP in diverse NSCLC histological types are confusing.…”

Pneumonitis Induced by Immune Checkpoint Inhibitors: From Clinical Data to Translational Investigation

“…A multi-institutional analysis suggested that the development of pneumonitis was significantly associated with increased progression-free survival (PFS) and overall survival (OS) in patients with advanced NSCLC treated with nivolumab (26). Nevertheless, some other studies found that treatment efficacy and survival were significantly decreased in patients with CIP compared with those without ICI therapy in NSCLC (5,27,28), while another retrospective study showed that no significant survival differences were seen with the occurrence of pneumonitis in metastatic melanoma treated with nivolumab (29).…”