Transformation in Marginal Zone Lymphoma: Results from a Prospective Cohort and a Meta-Analysis of the Literature

• The cumulative incidence of transformation in Marginal Zone Lymphoma is %5 at 5 years and 8% at 10 years after diagnosis.

• Transformation is associated with a 3.95-fold increased risk of death.

Marginal zone lymphoma (MZL) includes extranodal (EMZL), splenic (SMZL), and nodal (NMZL) subtypes. Histological transformation (HT) to large B-cell lymphomas is well documented but with a large variability in published cumulative incidence rates. We report results from the Molecular Epidemiology Resource (MER) cohort for the cumulative incidence of HT (with death as competing risk) and associated risk factors and outcomes. We also conduct a meta-analysis of available studies on the cumulative incidence of HT. From 2002-2015, 529 patients with MZL were enrolled in the MER (69% EMZL, 16% SMZL, 15% NMZL). Ten-year overall survival (OS) from diagnosis was 66%. HT occurred in 21 patients, with 5-year and 10-year cumulative incidence of HT of 2.7% (95% confidence interval [CI] 0.02-0.05) and 3.6% (95%CI 0.02-0.06), respectively. HT was associated with an increased risk of death (subdistribution hazard ratio (HR)=3.95; 95%CI 2.06-7.55). Predictors of HT were ≥2 extranodal sites and MALT-IPI score ≥2. OS was 79% at 5 and 55% at 10 years after HT. Age at HT≥70 years was the only predictor of OS after HT (HR=3.57; 95%CI 1.34-9.48). In meta-analysis of 12 studies (6,161 patients), the 5- and 10-year cumulative incidence of HT across all subtypes were 5% (95%CI 0.05-0.06) and 8% (95%CI 0.07-0.09), respectively. Rates were lower in EMZL (3% and 5%) than in SMZL (7% and 13%) and NMZL (9% and 13%). While HT is relatively uncommon in the first decade after MZL diagnosis, it is associated with an inferior outcome and needs new approaches to prevention and management.