P108 | EPIDEMIOLOGY AND CLINICAL CHARACTERISTICS OF RICHTER TRANSFORMATION: A SINGLE CENTER EXPERIENCE OF THE LAST 20 YEARS.

Richter transformation (RT) refers to the evolution of chronic lymphocytic leukemia (CLL) into an aggressive lymphoma, most commonly diffuse large B-cell lymphoma (DLBCL), less frequently Hodgkin lymphoma (HL). With the aim to identify the epidemiology, clinical features, and outcomes of patients (pts) with CLL who developed RT over a 20-year period, we retrospectively analyzed all consecutive pts diagnosed with RT between January 2004 and December 2024 at the Hematology Department of Spedali Civili, Brescia. Clinical, histopathological, genetic and survival data were collected. Fifty-four pts were analyzed. Median age at RT diagnosis was 70 years (range 45–83), and median time from CLL diagnosis was 6 years (range 0–221 months). Overall mean incidence of RT was 2.6 cases/year, increasing to 7.2 cases/year in the most recent period (2019–2024), with 12 cases in the last year, despite stable CLL incidence. Histologic subtypes included DLBCL (78%), HL (15%) and other (7%). Clonal relation to CLL was tested in 28 pts and confirmed in 26 (93%). Patients had received a median of 1.4 prior lines of CLL therapy (range 0–5) and 36% were treatment-naive. Prior therapies included chemoimmunotherapy (CIT) (33%), CIT combined with targeted therapy (TT) (40%), and TT alone (27%). Median time to transformation was 84 months for CIT-treated pts, 81 months for CIT+TT, and 55 months for TT alone. Median number of RT treatment lines was 1 (range 0–4). First-line RT treatment consisted of CHOP-like regimens in 41 pts (76%), radiotherapy alone in 2 pts (4%) with localized disease, ABVD in 3 pts (5%), a chemo-free combination (obinutuzumab, atezolizumab, venetoclax) in 2 (4%), and palliative care in 4 (7%); 2 pts (4%) died before receiving any treatment. With a median follow-up of 11 months (range 0–179) median progression-free (PFS) and overall survival (OS) were 24 and 56 months respectively. No significant difference in PFS or OS was observed between treatment strategies or histologic subtypes. PFS and OS were significantly shorter in patients with advanced-stage RT, prior CLL therapy or TP53 aberrations (p<0.02). In conclusion, RT still represent an unmet need. A more favorable outcome was observed in treatment-naive pts and in those with localized disease and without TP53 alterations. The increased incidence observed in recent years may be due to prolonged survival of high-risk CLL pts treated with TT. This observation should be confirmed in future studies and larger samples.