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

BMC Med. 2022 Oct 25;20(1):369. doi: 10.1186/s12916-022-02562-3.

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.

Keywords: Circulating tumor DNA; Diffuse large B cell lymphoma; Minimal residual disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / genetics
  • Circulating Tumor DNA* / genetics
  • Humans
  • Lymphoma, Large B-Cell, Diffuse* / diagnosis
  • Lymphoma, Large B-Cell, Diffuse* / drug therapy
  • Lymphoma, Large B-Cell, Diffuse* / genetics
  • Neoplasm Recurrence, Local
  • Positron Emission Tomography Computed Tomography
  • Prognosis

Substances

  • Circulating Tumor DNA
  • Biomarkers, Tumor