Venetoclax in Combination With Chemo‐Immunotherapy in Richter Transformation: A Real‐Life Experience
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, M. Turoldo, M. C. Rossetti, F. Gaudio, F. ZajaABSTRACT
The prognosis of Richter Transformation (RT) with standard chemo‐immunotherapy (CIT) remains poor. Several previous experiences with Venetoclax (V) in combination with CIT demonstrated the feasibility and safety of V‐CIT based regimens in RT. This is a retrospective, observational multicenter study aimed to assess the efficacy and safety of the real‐life use of V‐CIT in the treatment of RT. Response assessments were evaluated according to the Lugano 2014 criteria. 20 consecutive patients treated with V‐CIT based regimens from October 2018 to July 2024, were included. Median age was 63.5 years (33–73), with 75% of males. 11/17 were IGHV unmutated and 8/18 carried a mutation for Tp53 and/or a del17p. The median time from CLL diagnosis to RT was 6.5 years (0–17). A clonal relationship was demonstrated in 16/16 evaluable patients. The median number of prior treatments for CLL was 2 (0–4): CIT in 10, BTKi in 10, V based treatment in 4, no previous therapy in 5. V was associated with R‐DA‐EPOCH, R‐CHOP, and BFM in 10, 9 and 1 patients for a median number of 4 cycles (1–6). ORR was 55% with 10 CR (50%) and 1 PR (5%). 3 patients had progressive disease (PD) and 1 died for multiorgan failure. 7 patients received allogeneic‐HSCT consolidation. At a median follow up of 11.5 months (1–78), 10 patients, including 5 who received HSCT, are alive in CR; median PFS and OS were not reached. All patients 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%). Data from this real‐life experience confirm the feasibility and the activity of V‐CIT based combination in younger fit RT patients, where the high rate of initial response may allow a significant proportion to receive allogeneic‐HSCT consolidation. New studies with V combinations are ongoing and the comparison with this real‐life data may be worthwhile to better understand their therapeutic impact.