P111 | VENETOCLAX IN COMBINATION WITH CHEMOTHERAPY IN RICHTER SYNDROME PATIENTS: A REAL-LIFE EXPERIENCE

BACKGROUND: The prognosis of Richter Transformation (RT) with standard chemoimmunotherapy (CIT) remains poor. A previous study with Venetoclax (V) in combination with R-DA-EPOCH in 26 RT pts demonstrated an ORR of 62% with a median PFS and OS of 10.1 and 19.6 months respectively. Other subsequent experiences demonstrated the feasibility and safety of V based regimens in RT. AIMS: This is a retrospective, multicenter study aimed to assess the efficacy and safety of the off-label use of V plus CIT in the treatment of RT. METHODS: All previously untreated RT pts, who received at least one cycle of V in combination with CIT, were included. We collected data about CLL, type of RT treatment. Response assessments were evaluated according to the Lugano 2014 criteria. RESULTS: 20 RT pts from 9 Italian centers, treated with V-based regimen from October 2018 to July 2024, were included. Median age was 63.5 years (33-73), with 75% of males. 11/17 pts were IGHV unmutated and 8/18 patients carried a mutation for Tp53 and/or a del17p. The median number of prior treatments for CLL was 2 (0-4) wich included: CIT in 10, BTKi in 10, V based-treatment in 4; 5 pts were previously untreated. The median time from CLL diagnosis to RT was 6.5 years (0-17). The clonal relationship was available and demonstrated in 16 pts. V was associated with R-DA-EPOCH, R-CHOP, and BFM in 10, 9 and 1 pts respectively. Pts received a median number of 4 cycles (1-6). After at least 2 cycles ORR was 70% with 8 CR, 6 PR and 1 SD; 5 pts had a PD and 1 patient died after a cycle of R-DA-EPOCH for multiorgan failure. At the end of treatment ORR was 55% with 10 CR (50%), 1 PR (5%). 7 pts received allo-HSCT consolidation. At a median follow up of 11.5 months (1-78), 10 pts (including 5 who received HSCT) are alive in CR; median PFS and OS were not reached. All pts experienced grade 3-4 hematological toxicities: neutropenia (100%), anemia (50%) and thrombocytopenia (25%). Non-hematological toxicities included: febrile neutropenia (15%), covid19 (25%), other infections (30%), nausea (10%), thrombotic/hemorrhagic events (10%). CONCLUSIONS: data from this real-life experience are in line with previous studies confirming the feasibility and the activity of V based combination in younger fit RT pts, where the high rate of initial response may bridge a significant proportion to allo-HSCT. New ongoing studies with V combinations are ongoing and the comparison with this real-life data may be worthwhile to better understand their therapeutic impact.