B03 | Clonal hematopoiesis in follicular lymphoma: analysis of the phase III FIL FOLL12 trial

Background: Clonal Hematopoiesis (CH) is an age-related phenomenon, characterized by somatic mutations in hematopoietic stem cells involved in myeloid malignancies in individuals without myeloid neoplasms. The clinical interplay between CH and follicular lymphoma (FL), has not been fully elucidated yet.Methods: The study analyzed 242 FL patients treated with RCHOP or BR in the phase III FIL FOLL12 trial. Genomic DNA from baseline (N=242) and sequential samples (N=211) were available from whole peripheral blood and assessed for CH using CAPP-Seq-based NGS. The gene panel included 28 CH-related genes and a 1% VAF was set for variant calling. Clonal fitness (s, per year) was estimated from weighted regression on logit-transformed VAF. Clones were classified as increasing (s > 0.25/yr), decreasing (s < –0.25/yr), or stable when the 95% CI included zero.Results: At baseline, CH mutations were identified in 88 cases (36.4%) with DNMT3A (16.9%) and TET2 (12.0%) being the most common affected genes. CH+ patients had a significantly higher median age of 66 years compared to 57 for CH- patients (P