Access to novel therapies for chronic lymphocytic leukemia (CLL) varies throughout Latin America. Many centers still rely on chemoimmunotherapy (CIT) or suboptimal regimens due to cost and availability issues. Real-world data comparing CIT and targeted therapies in this region are limited and urgently needed to inform clinical decisions and policy.

Compare efficacy CIT and targeted therapies in CLL patients in Latin America.

We conducted a retrospective analysis of CLL patients who received first-line therapy in 11 Latin American countries (Argentina, Brazil, Chile, Colombia, Cuba, Guatemala, Mexico, Paraguay, Peru, Uruguay, and Venezuela) between 2010 and 2024. We grouped treatment regimens into six categories: a) venetoclax- based combinations with or without anti-CD20 antibodies; b) Bruton tyrosine kinase (BTK) inhibitors; c) standard CIT, including fludarabine, cyclophosphamide, and rituximab (FCR), or bendamustine and rituximab (BR); d) fludarabine and cyclophosphamide without rituximab (FC); e) rituximab or obinutuzumab combined with chlorambucil (R/G-chlorambucil); and f) suboptimal regimens, including chlorambucil monotherapy, R-CHOP, R-CVP, or any other nonstandard or unsupported combinations. Patients with less than 3 months of follow-up were excluded. We analyzed progression-free survival (PFS) to explore the impact of treatment backbone on outcomes.

Of the 2,175 patients who received treatment after 2010, the most common guideline-recommended regimens were FCR or BR (n = 528; 24.3%), BTK inhibitors (n = 198; 9.1%), chlorambucil plus anti-CD20 (n = 179; 8.2%), and venetoclax-based regimens (n = 97; 4.5%). However, 912 patients (41.9%) received suboptimal therapies, most commonly chlorambucil monotherapy (n = 561; 25.8%), FC (n = 261; 12.0%), and lymphoma-like regimens, such as CHOP or CVP ± anti-CD20 (n = 304; 14.0%). The median follow-up was 37 months (range, 3–167). Progression-free survival (PFS) at 3 years was 56%, with median PFS not reached. When stratified by treatment group, the 3-year PFS was 75% for venetoclax-based regimens, 71% for FCR/BR, 65% for BTK inhibitors, 59% for FC, 46% for R/G-chlorambucil, and 41% for suboptimal regimens. FISH testing for del(17p) and/or TP53 mutation was performed in 773 patients (35.5%), with abnormalities identified in 107 patients (13.8%). Of those, 68 patients (54%) received targeted therapies (venetoclax- or BTK-based), while 49 (46%) received CIT or other treatments.

This real-world analysis reinforces the urgent need to abandon the use of non-CLL-directed regimens such as CHOP or CVP as well as chlorambucil monotherapy in the treatment of patients with CLL. Adding anti-CD20 antibodies significantly improved outcomes for FC-based regimens. Notably, FCR and targeted agents (venetoclax or BTK inhibitors) demonstrated similar efficacy in this diverse Latin American patient population. However, this observation should be interpreted with caution, given the retrospective nature of the data and potential differences in patient selection and baseline risk profiles. The continued use of suboptimal, non-guideline-concordant regimens demonstrates an urgent need to increase access to modern therapies and improve medical education to promote evidence-based CLL care in Latin America.