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

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.

Circulating-tumor DNA Assessment in Diffuse Large B-cell Lymphoma to Determine Up-front Stem Cell Transplantation: A Pilot Study

“…Similar to our study results, Davide et al analyzed the clinical significance of the changes in ctDNA genotype during R-CHOP therapy in which new mutations appeared in the ctDNA in patients who were primarily refractory to R-CHOP or relapsed after treatment in the longitudinal monitoring of DLBCL genotype using ctDNA (10). Other studies mainly focused on the quantitative level of ctDNA as a tumor volume (11,26,28). Kurtz DM et al measured ctDNA level during treatment in 217 patients with DLBCL, and in most patients, ctDNA was detectable.…”

Circulating Cell-Free DNA as a Biomarker for Prognosis and Response to Systemic Therapy in Patients with Unresectable Hepatocellular Carcinoma

“…Increased levels of cfDNA have been observed in cancer patients and it is contemplated that cfDNA may harbor genomic alterations that are present in the original tumor, namely, circulating tumor DNA (ctDNA) [21]. The clinical validity of ctDNA has been reported in stratifying the prognosis of advanced cancer [18,[22][23][24]. Although next-generation sequencing can detect patient-specific somatic mutations in multiple genes, this technique is costly and time-consuming.…”

Dynamic monitoring of circulating tumor DNA reveals outcomes and genomic alterations in patients with relapsed or refractory large B-cell lymphoma undergoing CAR T-cell therapy

“…[5][6][7][8][9][10] ctDNA quantification enables the prognostic risk stratification of patients undergoing first-line or salvage chemotherapy for LBCL before and during treatment. [10][11][12][13][14] In particular, previous studies have indicated that both baseline and interim ctDNA measurements by the next-generation sequence (NGS) method were valuable in identifying highrisk patients undergoing chemoimmunotherapy. [15][16][17] Nevertheless, limited data exist on its applicability in patients receiving CAR T-cell therapy.…”