Circulating tumour DNA as a predictor of survival of patients with diffuse large B-cell lymphoma in a daily practice

Abstract

Diffuse large B-cell lymphoma (DLBCL) is a relatively well treatable disease with long-term cure rates between 60% and 70% following standard front-line immunochemotherapy R-CHOP (i.e. rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) or Pola-R-CHP (polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin and prednisone). Despite recent treatment advances, 30%-40% of DLBCL patients have primary refractory disease or experience a relapse; both associated with inferior survival outcomes. Importantly, none of the currently used prognostic tools can clearly identify these patients. Circulating tumour DNA (ctDNA) is a promising, non-invasive biomarker that has demonstrated prognostic value across multiple cancer types, including DLBCL. Prior studies have shown that ctDNA levels at diagnosis correlate with key DLBCL characteristics, such as clinical stage, serum lactate dehydrogenase (LDH) levels and international prognostic index (IPI) score. Early ctDNA clearance during treatment has been associated with better response rates and superior survival outcomes in DLBCL patients. However, further real-world data as well as randomized clinical trials are needed to support full ctDNA clinical integration for personalized DLBCL therapy. Therefore, we have analysed 44 DLBCL patients (Table S1), all treated with R-CHOP as a first-line chemoimmunotherapy and determined the baseline ctDNA levels and its dynamics using the CAncer Personalized Profiling by deep Sequencing approach and a custom panel of 521 genes. Methodological details are described in Supporting Informatio S1.