17th International Conference on Malignant Lymphoma, Palazzo dei Congressi, Lugano, Switzerland, 13 - 17 June, 2023.

Abstract

Introduction: Circulating tumor DNA (ctDNA) has been proven to be a promising tumor-specific biomarker in tumors, but its clinical utility in risk stratification and early prediction of relapse for peripheral T cell lymphoma (PTCL) has not been well explored. Methods: Using a lymphoma-specific sequencing panel, we assessed the prognostic and predictive utilities of ctDNA measurements before and after first-line therapy in 41 PTCL patients. Results: For the 41 patients, we obtained a total of 36 primary tumor specimens, 41 pretreatment blood samples and 21 serial blood samples before and after first-line therapy. By the last visit in March 2023, the median follow-up duration was 10.0 (range, 2.5–18.8) months. The clinical characteristics of the 41 patients were shown in Figure 1A. All patients received CHOP-like regimen. The top 30 somatic mutations of tissues were shown in Figure 1B. Pretreatment ctDNA (Pre-ctDNA) achieved an overall sensitivity of 81.3% (159/196) in detecting variants verified in tumor, indicating that ctDNA is a reliable source for PTCL genotyping. In addition, ctDNA allowed for the identification of additional 98 somatic mutations that were undetectable in tumor gDNA, which demonstrated that ctDNA could overcome tumor spatial heterogeneity (Figure 1C). Pre-ctDNA burden was significantly associated with clinical characteristics, including extranodal involvement (P < 0.001), lactate dehydrogenase (LDH) levels (P < 0.001), age (P = 0.047), B symptoms (P = 0.038), stage (P = 0.008) and international prognosis index (IPI) score (P < 0.001) (Figure 1D). The cell-free (cfDNA) fragments profoundly reflects both genomic and chromatin characteristics. Our results suggested that all samples had a more prominent mono-nucleosomal fragments abundance (167 bp), whereas the samples of angioimmunoblastic T-cell lymphom (AITL) and the samples with high IPI scores or non-complete response (CR) in the mid-stage of treatment had a more prominent shift towards shorter cfDNA size (Figure 1E). Similarly, when we analyzed the response to treatment, significant decline in ctDNA levels was observed at end of treatment (EOT) in patients with CR compared with those who did not achieved CR. The 4 patients with CR and EOT ctDNA negative achieved continuous CR until now (Figure 1F). Furthermore, high pre-ctDNA levels presented unfavourable PFS (P = 0.002) and OS (P = 0.020) (Figure 1G). Multivariate cox regression analysis showed that high pre-ctDNA burden (P = 0.029) and TP53 mutation (P = 0.005) (Figure 1H). Subgroup analysis showed that patients without these 2 risk factors (Type 1) had longer PFS than the other patients with more than 0 risk factor (Type 2) (P < 0.001) (Figure 1I). Keywords: Aggressive T-cell non-Hodgkin lymphoma, Diagnostic and Prognostic Biomarkers No conflicts of interests pertinent to the abstract.