Risk of transformation by frontline management in follicular and marginal zone lymphomas: a US Population-based Analysis

• The 10-year HGT cumulative incidence rate was 4.87% in FL and 2.95% in MZL

• Upfront treatment reduced the risk of transformation in FL but not in MZL

Follicular lymphoma (FL) and marginal zone lymphoma (MZL) often have long overall survival (OS), however, high-grade transformation (HGT) to diffuse large B-cell lymphoma (DLBCL) markedly reduces survival. The roles of upfront treatment versus observation on the incidence and outcome of HGT remain unclear. Thus, we analyzed a SEER database to address this question. Patients diagnosed with FL grades 1-2 and MZL between 2000 and 2020 were included. Fine and Gray models estimated impact of covariates on HGT cumulative incidence and lymphoma-specific survival (LSS) and Cox regression on OS. HGT occurred in 4.2% of 23,384 FL and 2.5% of 20,530 MZL patients. The 5- and 10-year HGT cumulative incidence rates were 2.80% and 4.87% for FL, and 1.74% and 2.95% for MZL, respectively, which are notably lower than in earlier studies. The annual HGT incidence rate peaked in the first two years, then steadily declined over two decades for FL and all MZL subtypes. In FL, upfront observation versus treatment increases HGT risk (SHR 1.23; 95%CI: 1.09-1.40, p<0.001) and barely affects OS (HR 0.95; 95%CI 0.90-0.99, p=0.03). Conversely, upfront observation was associated with lower HGT risk in nodal (SHR 0.71; 95%CI: 0.53-0.94, p=0.01) and extranodal (SHR 0.64; 95%CI: 0.48-0.86, p=0.003) MZL and did not affect survival in extranodal disease (HR 0.94; 95%CI: 0.97-1.02, p=0.15). HGT was associated with decrease in LSS across all histologies. Upfront treatment reduced the risk of HGT only in FL but not MZL.