Radiographic Features and Prognosis of Early- and Late-onset Non-small Cell Lung Cancer Immune Checkpoint Inhibitor-related Pneumonitis

Abstract

Background: Immunotherapy is becoming a standard of care for non-small cell lung cancer (NSCLC). Checkpoint inhibitor-associated pneumonia (CIP) is a rare and potentially life-threatening event that can occur at any time during tumor immunotherapy. However, there may be differences in the radiological patterns and prognosis of CIP during different periods. This study aimed to investigate the radiographic features and prognosis of early- and late-onset immune-related pneumonitis. Methods: We retrospectively analyzed the clinical data of 677 NSCLC patients receiving immunotherapy to identify 32 patients with CIP who were being effectively treated by hormonotherapy, analyzed the clinical and radiographic data, and summarized the radiological features and prognosis of early- and late-onset CIP. Results: CIP had an incidence of 4.7%, a median onset time of 2.4 months, and a mortality of 28.1%. Among these, CIP included 14 early-onset cases, where grade ≥3 CIP accounted for 92.9%, main radiographic pattern was organizing pneumonia (OP)-like pattern, and mortality was 50.0%. We also identified 18 late-onset CIPs, where grade ≥3 CIP accounted for 50.0%, main radiographic pattern was nonspecific interstitial pneumonia (NSIP)-like pattern, and mortality was 11.1%. The overall survival rate of the early-onset group was significantly lower than that of the late-onset group (P < 0.05).Conclusion: Early-onset CIP cases were higher in the National Comprehensive Cancer Network (NCCN) grade and mainly presented with an OP-like radiographic pattern; whereas, late-onset CIP cases were lower in NCCN grade and mainly presented with an NSIP-like radiographic pattern. Finally, the prognosis of the early-onset CIP group was poorer than that of the late-onset CIP group. We believe that this study will be helpful for clinicians for making early diagnosis and deciding treatment modalities for patients with CIP.

Risk Factors for Refractory Immune Checkpoint Inhibitor-related Pneumonitis in Patients With Lung Cancer

“…The onset of CIP was nonsignificantly earlier in the refractory group than in the nonrefractory group (16.57 vs. 7.43 wk, P =0.079). CIP with an onset ≤6 weeks and >6 weeks after ICI treatment was defined as early-onset and late-onset CIP, respectively 18,27. In addition, 92.9% of patients with early-onset CIP had grade 3 or higher CIP, with the mortality rate being as high as 50.0% 27.…”

“…18,27 In addition, 92.9% of patients with early-onset CIP had grade 3 or higher CIP, with the mortality rate being as high as 50.0%. 27 Early-onset CIP has a much poorer prognosis than late-onset CIP. Our study demonstrated that the incidence of early-onset CIP was higher in the refractory group than in the nonrefractory group (50.0% vs. 18.2%, P = 0.021), which could explain the higher mortality rate in the refractory CIP group.…”

“…CIP with an onset ≤ 6 weeks and > 6 weeks after ICI treatment was defined as early-onset and late-onset CIP, respectively. 18,27 In addition, 92.9% of patients with early-onset CIP had grade 3 or higher CIP, with the mortality rate being as high as 50.0%. 27 Early-onset CIP has a much poorer prognosis than late-onset CIP.…”

Chinese expert consensus on the multidisciplinary management of pneumonitis associated with immune checkpoint inhibitor

“…Chronic CIP is defined as persistent or worsening pneumonia after steroid reduction, and it is necessary to carry out immunosuppression for more than 12 weeks after ICI discontinuation 51 . Patients with early‐onset of CIP, within 6 weeks of ICI treatment, often have severe symptoms and poor prognosis, whereas patients with late‐onset of CIP, after 6 weeks of ICI treatment, often have few symptoms and better prognosis 52 …”

“…51 Patients with early-onset of CIP, within 6 weeks of ICI treatment, often have severe symptoms and poor prognosis, whereas patients with late-onset of CIP, after 6 weeks of ICI treatment, often have few symptoms and better prognosis. 52 The duration of CIP is variable from the beginning of ICI administration to withdrawal of the drug. Therefore, it is important to monitor CIP throughout the whole clinical process of ICI treatment.…”