Utility of serum Krebs von den Lungen-6 and surfactant protein-D levels for the diagnosis of immune checkpoint inhibitor-induced immune-related pneumonitis

Abstract

Background

Immune-related pneumonitis (irP) is a severe immune-related adverse event that can occur after treatment with immune checkpoint inhibitors (ICIs); accurate monitoring and early diagnosis are crucial. Serum Krebs von den Lungen-6 (KL-6) and surfactant protein-D (SP-D) are used to diagnose and monitor the disease activity of various types of interstitial lung disease. This study evaluated the usefulness of KL-6 and SP-D for diagnosing irP in cancer patients receiving ICIs.

Patients and methods

This retrospective observational study included cancer patients treated with more than two cycles of ICIs from September 2014 to October 2023. Receiver operating characteristic (ROC) analysis was used to assess the diagnostic utility of KL-6 and SP-D.

Results

Of the 724 cancer patients, 631 were included in the analysis, and 64 developed irP. The ROC analysis showed that KL-6 and SP-D had areas under the curve of 0.803 and 0.845, respectively. Serum KL-6 ≥ 500 U/mL had a sensitivity of 65.6% and a specificity of 83.4% for the diagnosis of irP, while SP-D ≥ 110 ng/mL had a sensitivity of 66.7% and a specificity of 88.6%. Combining both KL-6 ≥ 500 U/mL and SP-D ≥ 110 ng/mL resulted in a specificity of 96.6%, with a sensitivity of 46.7%. Combining either KL-6 ≥ 500 U/mL or SP-D ≥ 110 ng/mL resulted in a sensitivity of 85.0%, with a specificity of 75.5%. SP-D levels were significantly associated with irP severity, while KL-6 levels were not.

Conclusions

Serum KL-6 and SP-D are useful for diagnosing irP in cancer patients receiving ICIs.