P111 | Venetoclax in Combination With Chemotherapy in Richter Syndrome Patients: a Real-life Experience
Year: 2025
Type: article
Abstract: 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.
Authors: L. Ballotta, J. Olivieri, D. Facchinelli, I. Ferrarini, A. Visentin, R. Moia, M. Cavallari, V. Innao, E. Derenzini, P. M. Nierychlewska, A. Cuda, V. Gattei, M. Ballerini, E. Lucchini, F. Zaja
Institutions: Ospedale Maggiore, Azienda sanitaria universitaria Giuliano Isontina, Azienda sanitaria universitaria Friuli Centrale, Ospedale San Bortolo, University of Verona, University of Padua, Università degli Studi del Piemonte Orientale “Amedeo Avogadro”, Ospedale dell' Angelo, Ospedale Garibaldi, European Institute of Oncology, Ospedale di Cattinara, Centro di Riferimento Oncologico, University of Trieste
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7093121600
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