How to manage early-stage follicular lymphoma

Cencini, Emanuele; Fabbri, Alberto; Mecacci, Bianca; Bocchia, Monica

doi:10.1080/17474086.2020.1818226

Cited by 1 publication

(1 citation statement)

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“…Accordingly, newly diagnosed patients with FL and high tumor burden are typically treated with alkylator- or anthracycline-based chemoimmunotherapy. In contrast, patients with low-volume disease are treated with single-agent rituximab [ 27 – 29 ] or with watchful waiting until disease progression necessitates treatment [ 30 – 33 ], which occurs most frequently during the first five years [ 25 ]. Recent analysis continues to show that prompt treatment of early FL does not result in an overall survival benefit [ 25 , 33 ], but there is a continuing need to identify patients who will do worse and could potentially benefit from earlier treatment.…”

Section: Introductionmentioning

confidence: 99%

Relationship between BCL2 mutations and follicular lymphoma outcome in the chemoimmunotherapy era

et al. 2023

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How to identify follicular lymphoma (FL) patients with low disease burden but high risk for early progression is unclear. Building on a prior study demonstrating the early transformation of FLs with high variant allele frequency (VAF) BCL2 mutations at activation-induced cytidine deaminase (AICDA) sites, we examined 11 AICDA mutational targets, including BCL2, BCL6, PAX5, PIM1, RHOH, SOCS, and MYC, in 199 newly diagnosed grade 1 and 2 FLs. BCL2 mutations with VAF ≥20% occurred in 52% of cases. Among 97 FL patients who did not initially receive rituximab-containing therapy, nonsynonymous BCL2 mutations at VAF ≥20% were associated with increased transformation risk (HR 3.01, 95% CI 1.04–8.78, p = 0.043) and a trend toward shorter event-free survival (EFS, median 20 months with mutations versus 54 months without, p = 0.052). Other sequenced genes were less frequently mutated and did not increase the prognostic value of the panel. Across the entire population, nonsynonymous BCL2 mutations at VAF ≥20% were associated with decreased EFS (HR 1.55, 95% CI 1.02–2.35, p = 0.043 after correction for FLIPI and treatment) and decreased overall survival after median 14-year follow-up (HR 1.82, 95% CI 1.05–3.17, p = 0.034). Thus, high VAF nonsynonymous BCL2 mutations remain prognostic even in the chemoimmunotherapy era.

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