624MO - Retrospective analysis of clinical value of ctDNA in newly diagnosed diffuse large B cell lymphoma

Background

Diffuse Large B Cell Lymphoma (DLBCL) is the most common type of non-Hodgkin's lymphoma with high incidence, strong clinical and genetic heterogeneity. Current clinical characteristics are insufficient for the prognostic stratification of DLBCL. In recently, circulating tumor DNA (ctDNA) emerging as a biomarker for DLBCL prognostic stratification. However, whether it could use ctDNA as a biomarker to detect mutated genes in samples from Chinese DLBCL patients is uncertain.

Methods

The present study evaluated ctDNA as prognostic value for clinical diagnosis prior to treatment. We enrolled 172 newly diagnosed DLBCL patients, and all patients underwent targeted NGS-based 59-gene panel. The prognostic value of ctDNA in the context of established risk factors, including the International Prognostic Index, Ann Arbor stage, Lactate Dehydrogenase level (LDH), BULK, and bone marrow involvement (BMI), were evaluated. Finally, effects of pretreatment ctDNA on outcome of DLBCL were assessed.

Results

Before therapy, ctDNA was detectable in 74.4% of patients. The most frequently mutated genes were PCLO (33.6%) and PIM1 (32.8%). The mutation frequencies of KMT2D, CREBBP, BCL2, TP53, KLHL6 and MYC in GCB were significantly higher than in Non-GCB (p=0.012; 0.011; 0.036; 0.020; 0.0056). Whereas, CD79B mutation was more frequent in Non-GCB (p=0.023). The mean of pretreatment ctDNA variant allele frequencies (VAF) was significantly associated with both International Prognostic Index (IPI) and Ann Arbor stages; and we observed a significantly higher VAF mean among patients with abnormal LDH (p＜0.0001), with bone marrow involvement (p=0.0277), and with the bulk (p=0.0047). Using 23% threshold of ctDNA VAF mean, patients with high levels had inferior rates of overall survival (OS) and progression-free survival (PFS) than those with low levels, and its association with OS was significant.

Conclusions

CtDNA could serve as a prognostic factor and a tumor specific biomarker for DLBCL in China. The most frequently mutated genes were PCLO. The level of pretreatment ctDNA VAF mean could predict therapy response and prognosis.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Shanxi Provincial Cancer Hospital.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.