Frontline therapy patterns and outcomes in chronic lymphocytic leukemia: A real-world, multicenter analysis from Latin America.
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.
Article Details
Authors (50)
Celso Arrais-Rodrigues
Ana Oliver
4CASMU, Montevideo, Uruguay
Maria Cugliari
4Instituto de Oncología A. Roffo-Facultad de Medicina UBA-CABA, Buenos Aires, Argentina
Luis Mario Villela Martinez
16Hospital Fernando Ocaranza, Hermosillo, Mexico
Macarena Roa
13Hospital del Salvador, Santiago, Chile
Lorena Cardozo
7Hospital Central del Instituto de Previsión Social, Asunción, Paraguay
Marialejandra Torres Viera
15Clinica Santa Sofia, Caracas, Venezuela
Denisse Castro
6Hospital Edgardo Rebagliati, Lima, Peru
Daniela Trujillo Loaiza
10Universidad Tecnológica de Pereira, Pereira, Colombia
Leila Perobelli
35Hospital de Transplantes Euryclides de Jesus Zerbini – Hospital Brigadeiro, Sao Paulo, Brazil
Anelys García Salgado
12Ivan Portuondo General Teaching Hospital, Artemisa, Cuba
Victoria Irigoin
6British Hospital, Montevideo, Uruguay/ CASMU, Montevideo, Uruguay, Montevideo, Uruguay
Sofía Rivarola
13Hospital Británico de Buenos Aires, Buenos Aires, Argentina
Virginia Lema Spinelli
4Servicio medico Integral, Montevideo, Uruguay
Jose Alvarez
Universidad del Rosario, Bogota, Colombia
Alana von Glasenapp
10Instituto de Previsión Social, Asunción, Paraguay
Camila Peña
2Hospital Del Salvador, Santiago de Chile, Chile
Sally Paredes
3Hospital Nacional Edgardo Rebagliati Martins. Lima, Perú, Lima, Peru
Valeria Buccheri
8ICESP – Instituto do Câncer do Estado de São Paulo, Faculdade de Medicina da Universidade de Sao Paulo, São Paulo, Brazil
Gislaine Duarte
17Universidade Estadual de Campinas (UNICAMP), Campinas, Brazil
Maura Colturato
14Hospital Amaral Carvalho, Jau, Brazil
Laura Fogliatto
19Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil
Ana Ines Landoni
6Hospital Maciel, Montevideo, Uruguay
Sabrina ranero Ferrari
4Hospital de Clínicas. Facultad de Medicina. Universidad de la Republica., Unidad Academica de Hematologia, Montevideo, Uruguay
Augusto Mirolli
22Complejo Médico Churruca-Visca, Buenos Aires, Argentina
Marta Zerga
Miguel Pavlovsky
6Fundaleu, Buenos Aires, Argentina
Nancy Cristaldo
2Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
Maria del Rosario Custidiano
13Instituto Alexander Fleming, Buenos Aires, Argentina
Fernando Perez-Jacobo
13Hospital Central Norte Pemex, Ciudad de Mexico, Mexico, Mexico, Mexico
Danielle De Farias
8A Beneficência Portuguesa de São Paulo, São Paulo, Brazil
Maria Orlova
9Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
Julio Pose Cabarcos
29Sanatorio Otamendi, Buenos Aires, Argentina
Fernando Barroso Duarte
16Hospital Universitário Walter Cantídio, Fortaleza, Brazil
Etelvina Macchiavello
26Clinica La Pequeña Familia, Junin, Argentina
Sérgio Fortier
32Santa Casa de Misericórdia de São Paulo, Sao Paulo, Brazil
Julia Laviano
27Clinica Centro, Junin, Argentina
Clarisa Pagano Vilar
34Hospital Dr I. Pirovano, Buenos Aires, Argentina
Nelson Hamerschlak
Vera Figueiredo
13Hospital do Servidor Publico do Estado de Sao Paulo − IAMSPE, Sao Paulo, Brazil
Rosa Rios Jimenez
7Hospital Dr Luis Díaz Soto, Cuba, Habana, Cuba
Arianna Robles
14Hospital General de Occidente, Guadalajara, Jal, MEX, Guadalajara, Mexico
Javier Retamales
14Grupo Oncológico Cooperativo Chileno de Investigación (GOCCHI), Santiago, Chile
Melanie Otañez
40Hospital General del Estado de Sonora, Hermosíllo, Mexico
German Stemmelin
8Hospital Británico de Buenos Aires, Buenos Aires, Argentina
Henry Idrobo
5Universidad Tecnológica de Pereira, Clinica Central del eje, Pareira, Colombia, Pereira, Colombia
Brady Beltran
6Hospital Edgardo Rebagliati, Lima, Peru
Jorge Castillo
1Dana-Farber Cancer Institute, Bing Center for Waldenstrom's Macroglobulinemia, Boston, United States
Luis Malpica
Carlos Chiattone
4Department of Medicine, Santa Casa Medicine School, Sao Paulo, Brazil