Comprehensive analysis of blood-based biomarkers for predicting immunotherapy benefits in patients with advanced non-small cell lung cancer

Cheol-Kyu Park; Hyung-Joo Oh; Min-Seok Kim; Bo-Gun Koh; Hyun-Ju Cho; Young-Chul Kim; Hyung-Jeong Yang; Ji-Young Lee; Sung-Min Chun; In-Jae Oh

doi:10.21037/tlcr-21-100

Comprehensive analysis of blood-based biomarkers for predicting immunotherapy benefits in patients with advanced non-small cell lung cancer

Transl Lung Cancer Res. 2021 May;10(5):2103-2117. doi: 10.21037/tlcr-21-100.

Authors

Affiliations

¹ Department of Internal Medicine, Chonnam National University Medical School and Hwasun Hospital, Jeonnam, Republic of Korea.
² Department of Artificial Intelligence Convergence, Chonnam National University, Gwangju, Republic of Korea.
³ Department of Medical Science, Asan Medical Institute of Convergence Science and Technology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea.
⁴ Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.

Abstract

Background: This study aimed to investigate the feasibility of using circulating tumor cells (CTCs), peripheral blood cells (PBCs), and circulating cell-free DNA (cfDNA) as biomarkers of immune checkpoint inhibitor treatment response in patients with advanced non-small cell lung cancer (NSCLC).

Methods: We recruited patients diagnosed with advanced NSCLC who received pembrolizumab or atezolizumab between July 2019 and June 2020. Blood was collected before each treatment cycle (C1-C4) to calculate absolute neutrophil count (ANC), neutrophil-to-lymphocyte ratio (NLR), derived NLR (dNLR), and platelet-to-lymphocyte ratio (PLR). CTCs, isolated using the CD-PRIME^TM system, exhibited EpCAM/CK+/CD45- phenotype in BioViewCCBS^TM. The cfDNA was extracted from plasma at the beginning of C1 and C4.

Results: The durable clinical benefit (DCB) rate among 83 response-evaluable patients was 34%. CTC, PBC, and cfDNA levels at baseline (C1) were not significantly correlated with treatment response, although patients with DCB had lower CTC counts from C2 to C4. However, patients with low NLR, dNLR, PLR, and cfDNA levels at C1 had improved progression-free survival (PFS) and overall survival (OS). Patients with decreased CTC counts from C1 to C2 had higher median PFS (6.2 vs. 2.3 months; P=0.078) and OS (not reached vs. 6.8 months, P=0.021) than those with increased CTC counts. Low dNLR (≤2.0) at C1 and decreased CTC counts were independent factors for predicting survival.

Conclusions: Comprehensive analysis of CTC, PBC, and cfDNA levels at baseline and during treatment demonstrated they might be biomarkers for predicting survival benefit. This finding could aid in risk stratification of patients with advanced NSCLC who are undergoing immune checkpoint inhibitor treatment.

Keywords: Circulating tumor cells (CTCs); biomarkers; immune checkpoint inhibitor; non-small cell lung cancer (NSCLC).