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.

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.

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 2020 and 2024. Patients with <3 months of follow-up or incomplete data were excluded.

A total of 186 patients were analyzed. Median age was 64 years (range 37–92). Elevated β2-microglobulin was seen in 70% of the 97 tested. IGHV status was available for 111 patients (60%), with 71 (62%) unmutated. del(17p) and/or TP53 mutation was available in 126 patients (54%), with 5 (4%) positive. Venetoclax-based regimens were used in 47 patients (25%): 28 received VenO and 19 VenR. CIT was used in 75%: FCR in 81 (44%), R-chlorambucil in 34 (18%), G-chlorambucil in 8 (5%), and R-bendamustine in 15 (8%). After a median follow-up of 16 months (range 3-61), median time to next treatment (TTNT) was not reached in all groups except R-chlorambucil (16 months). TTNT at 2 years was 35% for anti-CD20 plus chlorambucil, 78% for R-bendamustine or FCR, 74% for VenR, and 73% for VenG. TTNT was slightly higher with venetoclax-based regimens (73%) versus CIT (64%), although not statistically significant (p = 0.08).

In this real-world Brazilian cohort, venetoclax-based regimens showed favorable outcomes and manageable toxicity compared to CIT in the frontline setting, including among high-risk patients. These results support the expanding role of time-limited targeted regimens in clinical practice and stress the importance of access to novel fixed-duration therapies in resource-limited environments.