Clinical implications of circulating tumor DNA in predicting the outcome of diffuse large B cell lymphoma patients receiving first-line therapy

• DOI: 10.1186/s12916-022-02562-3
• Publication Date: 2022-10-25T00:03:08Z
• Authors: Miaomiao Li; Lan Mi; Chunyang Wang; Xiaojuan Wang; Jianhua Zhu; Fei Qi; Hui Yu; Yingying Ye; Dedao Wang; Jiaowu Cao; Dingyao Hu; Quanyu Yang; Dandan Zhao; Tonghui Ma; Yuqin Song; Jun Zhu
• Keywords: Biophysics; Plant Biology; Diffuse large B cell lymphoma; FOS: Health sciences; Circulating Tumor DNA; 03 medical and health sciences; 0302 clinical medicine; Positron Emission Tomography Computed Tomography; FOS: Mathematics; Genetics; Biomarkers, Tumor; Humans; Molecular Biology; Cancer; Pharmacology; Circulating tumor DNA; Minimal residual disease; R; Cell Biology; Prognosis; 3. Good health; FOS: Biological sciences; 110309 Infectious Diseases; 19999 Mathematical Sciences not elsewhere classified; Medicine; Lymphoma, Large B-Cell, Diffuse; Neoplasm Recurrence, Local; Biotechnology; Research Article

Abstract

Background Circulating tumor DNA (ctDNA) has been proven to be a promising tumor-specific biomarker in solid tumors, but its clinical utility in risk stratification and early prediction of relapse for diffuse large B cell lymphoma (DLBCL) has not been well explored.

Methods Here, using a lymphoma-specific sequencing panel, we assessed the prognostic and predictive utilities of ctDNA measurements before, during, and after first-line therapy in 73 Chinese DLBCL patients.

Results The pretreatment ctDNA level serving as an independent prognostic factor for both progression-free survival (PFS, adjusted HR 2.47; p = 0.004) and overall survival (OS, adjusted HR 2.49; p = 0.011) was confirmed in our cohort. Furthermore, the patients classified as molecular responders who presented a larger decrease in ctDNA levels after the initial two treatment cycles had more favorable PFS (unreached vs. 6.25 months; HR 5.348; p = 0.0015) and OS (unreached vs. 25.87; HR 4.0; p = 0.028) than non-responders. In addition, interim ctDNA clearance may be an alternative noninvasive method of positron emission tomography and computed tomography (PET-CT) for predicting better PFS (HR 3.65; p = 0.0033) and OS (HR 3.536; p = 0.016). We also demonstrated that posttreatment ctDNA was a sensitive indicator for detecting minimal residual disease (MRD) in patients with a high risk of recurrence (HR 6.471; p = 0.014), who were otherwise claimed to achieve radiographic CR (complete remission).

Conclusions CtDNA is a promising noninvasive tool for prognosis prediction, response assessment, and early relapse prediction of first-line treatment in DLBCL patients.