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

Background Serum Krebs von den Lungen-6 (KL-6) and surfactant protein D (SP-D) are established biomarkers of interstitial lung diseases. However, their utility for differential diagnosis of immune checkpoint inhibitor-related pneumonitis (ICI-P) remains unclear.Methods This retrospective observational study included cancer patients who newly developed pulmonary diseases and in whom serum KL-6 and/or SP-D levels were measured at disease onset.Results Among 200 eligible patients, 77 had ICI-P and 123 had other pulmonary diseases (bacterial pneumonia, n = 64; lymphangitic carcinomatosis, n = 42; pulmonary edema, n = 10; radiation pneumonitis, n = 5; and others, n = 2). Serum KL-6 and SP-D levels were significantly higher in patients with ICI-P than in those without (both p < 0.001). The area under the receiver operating characteristic curve was 0.684 for KL-6 and 0.771 for SP-D. KL-6 ≥500 U/mL showed sensitivity and specificity of 0.623 and 0.705, respectively, and SP-D ≥110 ng/mL showed sensitivity and specificity of 0.693 and 0.769, respectively. When both KL-6 ≥500 U/mL and SP-D ≥110 ng/mL, the sensitivity and specificity were 0.480 and 0.907, respectively.Conclusions KL-6 and SP-D may play a supportive role in the differential diagnosis of ICI-P.