BTK and BCL-2 Inhibitors in the First-Line Treatment of Chronic Lymphocytic Leukemia in High-Risk Patients: Systematic Review and Network Meta-Analysis

• Autor(a) principal: Albuquerque, Rita de Cássia Ribeiro de
• Data de Publicação: 2024
• Outros Autores: Vieira, Cláudia Lima, Santiago, Isabel Cristina de Almeida, Nascimento, Aline do, Chança, Raphael Duarte, Tura, Bernardo Rangel, Correia, Marcelo Goulart, Barufaldi, Laura Augusta
• Tipo de documento: Artigo
• Idioma: por; eng
• Título da fonte: Revista Brasileira de Cancerologia (Online)
• Texto Completo: https://rbc.inca.gov.br/index.php/revista/article/view/4501
• topic: Leucemia Linfocítica Crônica de Células B; Inibidores de Proteína Tirosina Quinase; Protocolos Antineoplásicos; Revisão Sistemática; Metanálise em Rede; Leukemia, Lymphocytic, Chronic, B-Cell; Tyrosine Protein Kinase Inhibitors; Antineoplastic Protocols/venetoclax; Systematic Review; Network Meta-Analysis; Leucemia Linfocítica Crónica de Células B; Inhibidores de la Tirosina Proteína Quinasa; Protocolos Antineoplásicos/venetoclax; Revisión Sistemática; Metaanálisis en Red

Introduction: Patients with high-risk chronic lymphocytic leukemia (CLL) have lower response rates, a more aggressive clinical course, and resistance to standard chemotherapy, representing a treatment challenge. Bruton's tyrosine kinase inhibitors (BTK – ibrutinib and acalabrutinib) and the BCL-2 inhibitor (venetoclax) can be used in these cases. Objective: To identify and evaluate studies on the efficacy and safety of the use of ibrutinib, acalabrutinib and venetoclax in first-line treatment in patients with high-risk CLL. Method: Systematic review of randomized clinical trials that evaluated adult patients with CLL, carriers of 17p deletion or TP53 mutation and without prior treatment. The PubMed, EMBASE, LILACS and Cochrane Library databases were searched, and the risk of bias was assessed using the Cochrane RoB 2 tool and the quality of evidence was assessed with GRADE. Results: In the network meta-analysis for progression-free survival (PFS) venetoclax + obinutuzumab (RR: 0.62; 95%CI 0.41-0.95; p value 0.027) and acalabrutinib + obinutuzumab (RR: 0. 74; 95% CI 0.55-0.99; p value 0.043) presented a lower risk of progression or death, with significance considered borderline. Ibrutinib + obinutuzumab (RR: 0.93; 95% CI 0.86-1.00; p value 0.054) did not show a significant difference in PFS for patients with high-risk CLL. Conclusion: First-line treatment with BTK inhibitors (ibrutinib and acalabrutinib) and the BCL-2 inhibitor (venetoclax) associated with anti-CD20 monoclonal agents – especially obinutuzumab – have been proposed as the standard for most patients with CLL. However, based on the results of this review with network meta-analysis, it was not possible to confirm this recommendation.