The clinical utility of plasma circulating tumor DNA in the diagnosis and disease surveillance in non-diffuse large B-cell non-Hodgkin lymphomas.

Aim: Advances in circulating tumor DNA (ctDNA) analysis for diffuse large B-cell lymphoma (DLBCL) have prompted the evaluation of its utility in other non-Hodgkin lymphomas (NHLs), leading to significant insights into its potential applications.

Methods

We retrospectively studied paired plasma and tissue/bone marrow biopsies of 203 non-DLBCL NHLs [87 follicular lymphomas (FL), 64 mantle cell lymphomas (MCL), 30 chronic lymphocytic leukemia/small lymphocytic lymphomas (CLL/SLL) and 22 marginal zone lymphomas (MZL)]. Genomic profiling was performed using a targeted next generation sequencing panel (Hemasalus™). Longitudinal analyses were performed to explore plasma ctDNA utility in disease monitoring.

Results

High plasma ctDNA detection rates were observed across NHL subtypes (FL: 88.5%, MCL: 90.6%, CLL/SLL: 100%, MZL: 68.2%), with high concordance of actionable mutations (FL: 87.4%, MCL: 93.8%, CLL/SLL: 93.3%, MZL: 81.8%) and multiple genetic aberrations exclusively identified in plasma. Particularly, IGH-BCL2 and IGH-CCND1 fusions were concordant between plasma and tumor biopsies in FLs (91.1%) and MCLs (91.3%), respectively. Longitudinal data demonstrated that ctDNA clearance correlated with complete response but ctDNA increases preceded radiological relapses.

Conclusion

ctDNA exhibited high concordance with tumor biopsy in detecting genetic aberrations and demonstrated potential as a promising noninvasive approach to disease surveillance in non-DLBCL NHLs.