Bronchoalveolar lavage cell percentages as diagnostic markers of immune checkpoint inhibitor pneumonitis

Mahnoor Mir^1*Felipe Soto²Pedro Gomez²Rodrigo Del Rio Arroyo²Adarsh Suresh³Amber Su⁴Qiong Gan⁴John Stewart⁴Roberto Adachi⁴Diwakar Balachandran⁴Lara Bashoura⁴Roberto Casal⁴Burton F Dickey⁴George Eapen⁴Scott E Evans⁴Horiana Grosu⁴Carlos A Jimenez⁴Julie Lin⁴David Ost⁴Bruce Sabath⁴Vickie Shannon⁴Aung Naing⁴Jianjun Gao⁴Jia Wu⁴Karthik Suresh⁵Saadia A Faiz⁴Mehmet Altan⁴Ajay Sheshadri⁴

• ¹University of Texas Health Science Center at Houston, Houston, United States
• ²School of medicine, Tecnológico de Monterrey,, Monterrey, Mexico
• ³Texas A and M University, College Station, Texas, United States
• ⁴University of Texas MD Anderson Cancer Center, Houston, Texas, United States
• ⁵Johns Hopkins Medicine, Johns Hopkins University, Baltimore, Maryland, United States

Diagnostic biomarkers for immune checkpoint inhibitor pneumonitis (ICIP) are lacking. Bronchoalveolar lavage (BAL) lymphocytosis has been associated with ICIP, but studies have not evaluated BAL lymphocytosis as a diagnostic biomarker for ICIP.To measure the association of BAL immune cell percentage with ICIP and test its performance as a diagnostic biomarker.We performed a retrospective chart review of 476 patients treated with ICI for solid organ or hematologic malignancies who underwent BAL between 2016 and 2022. Two independent reviewers, blinded to results of BAL cell percentage, confirmed the diagnosis of ICIP or other conditions (e.g., pneumonia) based on clinical history and radiology. We constructed logistic regression models to assess the relationship between BAL lymphocyte, eosinophil, and neutrophil percentages and the diagnosis of pneumonitis, and the area under the receiver-operator curves (AUROC) was used to assess their discriminatory function. We measured the association of BAL immune cell percentages with one-year overall survival using Cox proportional hazards models adjusted for age and cancer diagnosis.Each 1% increase in lymphocyte (OR 1.01, 95% CI 1.011.02, p < 0.001) and eosinophil percentage (OR 1.05, 95% CI 1.01-1.11, p = 0.01) were independently associated with pneumonitis, while neutrophil percentage was inversely associated (OR 0.99, 95% CI 0.98-0.99, p = 0.01) with pneumonitis. In multivariable analysis, lymphocyte percentage (OR 1.02, 95% CI 1.009-1.04, p = 0.002) and eosinophil percentage (OR 1.10, 95% CI 1.01-1.23, p = 0.05) were both associated with ICIP. The AUROC for BAL lymphocytes to diagnose ICIP was 0.62 (95% CI, 0.57-0.67, optimal cutoff 15.5%, sensitivity 69%, specificity 52%) and the AUROC for eosinophils was 0.61 (95% CI, 0.56-0.66, optimal cutoff 1%, sensitivity 58%, specificity 62%). In patients with pneumonitis, lymphocyte percentage (HR 0.99, 95% CI 0.97-1.00, p=0.02), neutrophil percentage (HR 1.01, 95% CI 1.00-1.02, p=0.05), and eosinophil percentage (HR 0.93, 95% CI 0.86-0.99, p=0.03) were associated with one-year survivalBAL lymphocytosis and eosinophilia are associated with ICIP, but their ability to discriminate ICIP from other conditions is modest. BAL immune cell percentages may have prognostic value for one-year survival, but this likely reflects the morbidity of other pulmonary diseases that require BAL for evaluation.