DP051 | VENETOCLAX-RITUXIMAB FIXED DURATION TREATMENT IN PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA AFTER BTK-INHIBITORS OR CHEMIO-IMMUNOTHERAPY FAILURE: EFFICACY AND SAFETY RESULTS OF A RETROSPECTIVE MULTICENTER STUDY FROM THE REGIONAL CAMPANIA NETW

In both first line and relapsed/refractory (R/R) settings, targeted agent-based therapies, such as venetoclax plus Rituximab (R) and covalent Bruton tyrosine kinase inhibitors (BTKis), have outperformed chemoimmunotherapy (CHT-I) in treating pts (pts) with chronic lymphocytic leukaemia (CLL). Nevertheless, information is still lacking in terms of guiding the best sequencing of treatments. For this reason, we undertook a multicentre retrospective study providing a large series of R/R CLL scheduled to receive time-limited VenR for 24 months in all Hematology Units of the regional Campania network, assessing efficacy and safety after BTKi or CHT-I failure. The primary endpoint was overall response rate (ORR) at 24mos. Secondary endpoints were PFS, OS, toxicity and feasibility of VenR schedule. A total of 75 pts scheduled to receive VenR from June 2020 to September 2024 were enrolled, in particular 54% were BTKis naïve and 46% received VenR after ibrutinib discontinuation (table 1). Overall, 61 pts completed the treatment for 24 mos since 3 pts are still receiving VenR and 11 (18%) permanently discontinued for the following reasons: 1) progression disease (PD) in 4 pts; 2) death for reasons unrelated to the disease in 3 pts; 3) VenR-related adverse event (AE) in 3 pts; 4) clinician’s choice (1 young patient received allotransplant). The median duration of Ven exposure for pts discontinuing treatment was 12 mos (range, 7-18). The ORR for those completing the schedule was 100% (58 CR and 3 PR). Of the 58 pts with clinical parameters consistent with CR, computed tomography and peripheral blood minimal residual disease evaluation by flow cytometry was performed in 44 (76%) pts showing CR. The overall PFS with a median follow-up of 31 mos (range, 7-49) from VenR was 75% and OS was 81%. In addition, PFS was stratified according to BKTi exposure, and the log-rank test analysis was significant (p value= 0.04) with 24-month PFS of 100% in BTKis-naïve vs 82% in BTKis exposed. As for VenR safety and feasibility we collected data regarding discontinuation for AE, dosage reduction and total number of R infusions (table 2). Univariate analyses found no significant correlation between clinico-pathologic variables and VenR schedule modification with PFS (other than BKTi exposure), but prior bendamustine exposure seems to correlate with more discontinuation due to neutropenia event, febrile neutropenia and pneumonitis. Herein, we report, to our knowledge, the largest series of pts receiving fixed-time VenR for both cBTKi and CHT-I exposed CLL. VenR appears as effective treatment in both cases achieving an ORR of 100% in those completing the schedule, although PFS appears shorter in cBTKi exposed. In addition, deviation from standard schedule with pts-tailored dosages of both Ven and R, does not seem to impact ORR and PFS.