First-line venetoclax-based regimens versus chemoimmunotherapy in chronic lymphocytic leukemia: A real-world analysis from the brazilian CLL registry

Abstract Background: Venetoclax, a selective BCL-2 inhibitor, has transformed the treatment of chronic lymphocytic leukemia (CLL). Randomized trials such as CLL14 and CLL13 have demonstrated the superiority of venetoclax-obinutuzumab (VenO) over chemoimmunotherapy in both elderly and younger, fit patients. To contextualize these findings in real-world settings, we conducted a retrospective analysis of first-line treatment data from the Brazilian CLL Registry. We used the treatment arms and comparator groups from the CLL14 and CLL13 trials as a framework for our analysis across different healthcare sectors in Brazil. Our goal was to assess the effectiveness and safety of venetoclax-based regimens as a first-line therapy for CLL compared to standard CIT using real-world data from the Brazilian CLL Registry. Methods: This retrospective multicenter study included patients with CLL treated in the frontline setting with either venetoclax-based regimens (with or without anti-CD20 antibodies) or standard CIT (e.g., FCR, BR, or chlorambucil-based combinations) between 2016 and 2024. Patients with <3 months of follow-up or incomplete data were excluded. Results: A total of 482 patients were analyzed. Median age was 65 years (range 27–92). Elevated β2-microglobulin was seen in 63% of the 214 tested. IGHV status was available for 194 patients (40%), with 124 (63%) unmutated. del(17p) and/or TP53 mutation was available in 259 patients (54%), with 12 (5%) positive. Venetoclax-based regimens were used in 59 patients (12%): 37 received VenO and 22 VenR (4%). CIT was used in 88%: FCR in 230 (48%), R-chlorambucil in 87 (18%), G-chlorambucil in 67 (14%), and R-bendamustine in 39 (8%). After a median follow-up of 33 months, median time to next treatment (TTNT) was not reached in all groups except R-chlorambucil (28 months). Three-year TTNT rates were: R-chlorambucil 34%, G-chlorambucil 51%, R-bendamustine 78%, FCR 67%, VenR 77%, and VenG 83%. TTNT was significantly higher with venetoclax-based regimens (80%) versus CIT (58%, P=0.006). Three-year overall survival (OS) was similar (87% in both, P=0.75). Conclusion: Real-world data from this cohort allowed us to compare venetoclax-based regimens with CIT as first-line therapy for CLL, including high-risk patients. As expected, venetoclax-based regimens showed favorable results, and their use should be considered as an effective time-limited therapy, even in lower-middle-income countries. Updated analyses with longer follow-up and broader inclusion will be presented at the meeting.