ctDNA-adjusted bTMB as a predictive biomarker for patients with NSCLC treated with PD-(L)1 inhibitors.

Abstract

BACKGROUND:

In non-small cell lung cancer (NSCLC) patients receiving immune checkpoint inhibitors (ICIs), higher blood tumor mutational burden (bTMB) was usually associated with better progression-free survival (PFS) and objective response rate (ORR). However, the association between bTMB and overall survival (OS) benefit remains undefined. It has been reported that patients harboring a high level of circulating tumor DNA (ctDNA) had poor survival. We hypothesized that ctDNA-adjusted bTMB might predict OS benefit in NSCLC patients receiving ICIs.

METHODS:

Our study was retrospectively performed in three cohorts, including OAK and POPLAR cohort (n = 853), Shanghai and Wuhan (SH&WH) cohort (n = 44), and National Cancer Center (NCC) cohort (n = 47). Durable clinical benefit (DCB) was defined as PFS lasting ≥ 6 months. The cutoff value of ctDNA-adjusted bTMB for DCB prediction was calculated based on a receiver operating characteristic curve. Interaction between treatments and ctDNA-adjusted bTMB was assessed.

RESULTS:

The bTMB score was significantly associated with tumor burden, while no association was observed between ctDNA-adjusted bTMB with tumor burden. In the OAK and POPLAR cohort, significantly higher ORR (P = 0.020) and DCB (P < 0.001) were observed in patients with high ctDNA-adjusted bTMB than those with low ctDNA-adjusted bTMB. Importantly, the interactions between ctDNA-adjusted bTMB and treatments were significant for OS (interaction P = 0.019) and PFS (interaction P = 0.002). In the SH&WH cohort, the interactions between ctDNA-adjusted bTMB and treatment were marginally significant for OS (interaction P = 0.081) and PFS (interaction P = 0.062). Similar result was demonstrated in the NCC cohort.

CONCLUSIONS:

Our study indicated that ctDNA-adjusted bTMB might predict OS benefit in NSCLC patients receiving ICIs. The potential of ctDNA-adjusted bTMB as a noninvasive predictor for immunotherapy should be confirmed in future studies.

• Authors: Wei Nie, Zhi-Jie Wang, Kai Zhang, Bing Li, Yi-Ran Cai, Feng-Cai Wen, Ding Zhang, Yue-Zong Bai, Xue-Yan Zhang, Shu-Yuan Wang, Lei Cheng, Hua Zhong, Li Liu, Jie Wang, Bao-Hui Han
• Journal: BMC medicine (BMC Med) Vol. 20 Issue 1 Pg. 170 (05 05 2022) ISSN: 1741-7015 [Electronic] England
• PMID: 35509036 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022. The Author(s).

Chemical References

• Biomarkers, Tumor
• Circulating Tumor DNA

Topics

• Biomarkers, Tumor (genetics)
• Carcinoma, Non-Small-Cell Lung (drug therapy, genetics, pathology)
• China
• Circulating Tumor DNA (genetics)
• Humans
• Lung Neoplasms (drug therapy, genetics, pathology)
• Mutation
• Retrospective Studies