Frontline therapy patterns and outcomes in chronic lymphocytic leukemia: A real-world, multicenter analysis from Latin America.

Abstract Background: 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. Methods: We conducted a retrospective analysis of CLL patients who received first-line therapy in 10 Latin American countries (Argentina, Brazil, Chile, Colombia, Cuba, 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) and overall survival (OS) to explore the impact of treatment backbone on outcomes. Results: Of the 2,133 patients who received treatment after 2010, the most common guideline-recommended regimens were FCR or BR (n = 521; 24.4%), BTK inhibitors (n = 188; 8.8%), chlorambucil plus anti-CD20 (n = 177; 8.3%), and venetoclax-based regimens (n = 89; 4.2%). However, 899 patients (42.1%) received suboptimal therapies, most commonly chlorambucil monotherapy (n = 552; 25.9%), FC (n = 259; 12.1%), and lymphoma-like regimens, such as CHOP or CVP ± anti-CD20 (n = 300; 14.1%). To analyze outcomes in the era of targeted therapies, we included 1,282 patients treated between 2015 and 2024. The median follow-up was 34 months (range, 0–119). Progression-free survival (PFS) at 3 years was 51%, with median PFS not reached. When stratified by treatment group, the 3-year PFS was 75% for venetoclax-based regimens, 67% for FCR/BR, 65% for BTK inhibitors, 48% for FC, 43% for R/G-chlorambucil, and 33% for suboptimal regimens. FISH testing for del(17p) and/or TP53 mutation was performed in 571 patients (44.5%), with abnormalities identified in 77 patients (13.5%). Of those 77 patients, 50 (65%) received targeted therapies (venetoclax- or BTK-based), while 27 (35%) received CIT or other treatments. Conclusions: 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.

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Journal
Blood
Published
2025-11-03
DOI
https://doi.org/10.1182/blood-2025-2775
Primary Topic
Chronic Lymphocytic Leukemia Research
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article
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article

Frontline therapy patterns and outcomes in chronic lymphocytic leukemia: A real-world, multicenter analysis from Latin America.

Miguel Arturo Pavlovsky, Clarice Vilar, Maria Del Rosario Custidiano, Carlos Chiattone et al.
Blood
Chronic Lymphocytic Leukemia Research
article

Frontline therapy patterns and outcomes in chronic lymphocytic leukemia: A real-world, multicenter analysis from Latin America.

Miguel Arturo Pavlovsky, Clarice Vilar, Maria Del Rosario Custidiano, Carlos Chiattone, Melani Otañez, Nancy Cristaldo, Sofía Rivarola, Fernando Barroso Duarte, Valéria Buccheri, Vera Figueiredo, Rosario Jiménez, Jorge J. Castillo, María Silvana Cugliari, Alana Von Glasenapp, Javier Retamales, Julia Laviano, Etelvina Macchiavello, Leila Perobelli, Sally Paredes, Germán Stemmelin, Luis Mario Villela Martínez, Sérgio Costa Fortier, Camila Peña, Victoria Irigoin, Julio Pose Cabarcos, Laura Fogliatto, Danielle De Farias, Nelson Hamerschlak, Brady Beltrán, Denisse Castro, Ana Inés Landoni, Henry Idrobo, Fernando Pérez‐Jacobo, Luis Malpica, Macarena Roa, Anelys García Salgado, Jose Alvarez, Carolina Oliver, Marialejandra Torres Viera, Maura Colturato, María Orlova, Celso Arrais-Rodrigues, Laura Cardozo, Sabrina Ranero Ferrari, Gislaine Duarte, Arianna Robles, Marta Zerga, Virginia Lema Spinelli, Daniela Trujillo Loaiza, Augusto Mirolli
article en

Abstract

Abstract Background: 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. Methods: We conducted a retrospective analysis of CLL patients who received first-line therapy in 10 Latin American countries (Argentina, Brazil, Chile, Colombia, Cuba, 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) and overall survival (OS) to explore the impact of treatment backbone on outcomes. Results: Of the 2,133 patients who received treatment after 2010, the most common guideline-recommended regimens were FCR or BR (n = 521; 24.4%), BTK inhibitors (n = 188; 8.8%), chlorambucil plus anti-CD20 (n = 177; 8.3%), and venetoclax-based regimens (n = 89; 4.2%). However, 899 patients (42.1%) received suboptimal therapies, most commonly chlorambucil monotherapy (n = 552; 25.9%), FC (n = 259; 12.1%), and lymphoma-like regimens, such as CHOP or CVP ± anti-CD20 (n = 300; 14.1%). To analyze outcomes in the era of targeted therapies, we included 1,282 patients treated between 2015 and 2024. The median follow-up was 34 months (range, 0–119). Progression-free survival (PFS) at 3 years was 51%, with median PFS not reached. When stratified by treatment group, the 3-year PFS was 75% for venetoclax-based regimens, 67% for FCR/BR, 65% for BTK inhibitors, 48% for FC, 43% for R/G-chlorambucil, and 33% for suboptimal regimens. FISH testing for del(17p) and/or TP53 mutation was performed in 571 patients (44.5%), with abnormalities identified in 77 patients (13.5%). Of those 77 patients, 50 (65%) received targeted therapies (venetoclax- or BTK-based), while 27 (35%) received CIT or other treatments. Conclusions: 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.

BloodVol. 146(Supplement 1)
The University of Texas MD Anderson Cancer Center (US), Universidade Estadual de Campinas (UNICAMP) (BR), Universidad de Guadalajara (MX), BioClinica (United States) (US), Technological University of Pereira (CO), Universidad de Buenos Aires (AR), Hospital Israelita Albert Einstein (BR), Hospital Italiano de Buenos Aires (AR), Hospital Maciel (UY), Universidad de Sonora (MX), Irmandade da Santa Casa de Misericórdia de São Paulo (BR), Hospital do Servidor Público Municipal (BR), Hospital de Clínicas de Porto Alegre (BR), Hospital Samaritano de São Paulo (BR), Hospital del Salvador (CL), Hospital Universitário Walter Cantídio (BR), Hospital Amaral Carvalho (BR), Beneficência Portuguesa de São Paulo (BR), Hospital Oncológico Docente "Conrado Benítez García" (CU), Dana-Farber Cancer Institute (US), Gobierno de Chile (CL), Instituto Alexander Fleming (AR), Centro Médico ABC (MX), Spitalul Universitar de Urgenţă Militar Central Dr. Carol Davila (RO), Dr. Euryclides Hospital de Jesus Zerbini (BR), Asociación Psicoanalítica de Buenos Aires (AR), Hospital Alemán (AR), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (BR), Sanatorio Otamendi y Miroli (AR), Hospital Británico de Buenos Aires (AR), Associação Paulista de Medicina (BR), Universidad de Ciencias Médicas de la Habana (CU), El Colegio de Sonora (MX), Hospital de Clínicas (UY), St Martins Hospital (GB), Hospital São Paulo (BR), Universidad Hospital Italiano (AR), IPS Central (PY), Universidad de Montevideo (UY), Universidad Central de Venezuela (VE), Hospital Central Militar (MX), Tecnológico de Monterrey (MX)
Openalex Percentile: Top 43%
Chronic Lymphocytic Leukemia Research
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