Revisão sistemática da eficácia do Ibrutinibe em comparação com a Clorambucila no tratamento de primeria linha da leucemia linfocítica crônica
Revisão sistemática da eficácia do Ibrutinibe em comparação com a Clorambucila no tratamento de primeria linha da leucemia linfocítica crônica
Data
2025
Autores
El Adji, Samira
Journal Title
Journal ISSN
Volume Title
Publisher
Instituto Nacional de Cardiologia
Resumo
Introdução: A leucemia linfocítica crônica - LLC é uma neoplasia indolente
caracterizada pela proliferação e acúmulo de linfócitos B morfologicamente maduros,
mas imunologicamente disfuncionais. É o tipo mais comum de leucemia nas
populações ocidentais. O cenário atual do fornecimento de medicamentos
oncológicos pelo SUS ainda enfrenta desafios, apesar dos avanços recentes. Na
literatura, o tratamento da LLC é individualizado e pode incluir terapias-alvo como
inibidores da tirosina quinase de Bruton (BTK), quimioterapia e transplante de
células-tronco hematopoéticas. O ibrutinibe é um inibidor de BTK registrado no Brasil
para o tratamento da LLC. A clorambucila é, no momento, o medicamento mais
prescrito em unidades da Secretaria de Estado de Saúde do Rio de Janeiro.
Objetivo: Avaliar a eficácia do ibrutinibe em comparação com a clorambucila em
primeira linha de tratamento da LLC.
Método: Revisão sistemática de ensaios clínicos randomizados que avaliaram a
eficácia do ibrutinibe em comparação com a clorambucila em pacientes adultos com
LLC sem tratamento prévio. Foram pesquisadas as bases MEDLINE, EMBASE
LILACS e Cochrane Library (CENTRAL), bem como em bases de literatura cinzenta
como o Google Acadêmico, o catálogo de teses da CAPES, Biblioteca Digital
Brasileira de Teses e Dissertações (BDTD), Open Access Theses and Dissertations,
Mednar, World Wide Science e WorldCat. A avaliação do risco de viés foi realizada
pela ferramenta RoB 2 da Cochrane e para a certeza no conjunto das evidências foi
utilizada a ferramenta GRADE.
Resultados: A pesquisa resultou na identificação inicial de 2.228 títulos. Após a
remoção de duplicatas, 1.704 estudos foram submetidos à análise de títulos e
resumos. 2.373 registros foram avaliados em bases de literatura cinzenta, mas
nenhum foi incluído. Dessa análise, sete artigos avançaram para leitura integral, dos
quais seis foram excluídos por se tratarem de resumos de congresso ou registros de
um mesmo ensaio clínico. No fim, apenas o estudo RESONATE-2 atendeu aos
critérios de elegibilidade. O estudo RESONATE-2 foi um estudo clínico de fase III
que avaliou a eficácia e segurança do ibrutinibe em comparação com a clorambucila
como tratamento de primeira linha em pacientes com leucemia linfocítica crônica ou
linfoma linfocítico de pequenas células. Os resultados do estudo demonstraram que
o ibrutinibe é superior a clorambucila em termos de sobrevida livre de progressão
com uma taxa de 90% e uma taxa de sobrevida global de 98%.
Conclusão: A clorambucila é um medicamento com baixa representatividade na
literatura científica atual, apresentando menor eficácia e maior incidência no total de
eventos adversos em comparação ao ibrutinibe. Este último, um inibidor de tirosina
quinase de Bruton, que se destaca pela sua seletividade, melhor eficácia e um perfil
de segurança mais favorável em comparação com a clorambucila. Isto o torna uma
opção terapêutica no tratamento inicial da LLC. Assim e diante da aparente ausência
de uma diretriz nacional para essa doença, há evidências favoráveis sobre a eficácia
do medicamento, quando comparado a clorambucila.
Introduction: Chronic lymphocytic leukaemia (CLL) is an indolent neoplasm characterised by the proliferation and accumulation of morphologically mature but immunologically dysfunctional B lymphocytes. It is the most common type of leukaemia in Western populations. The current scenario for the supply of oncological drugs by the SUS still faces challenges, despite recent advances. In the literature, the treatment of CLL is individualised and can include target therapies such as Bruton's tyrosine kinase (BTK) inhibitors, chemotherapy and haematopoietic stem cell transplantation. Ibrutinib is a BTK inhibitor registered in Brazil for the treatment of CLL. Chlorambucil is currently the most prescribed drug in Rio de Janeiro State Health Department units. Objective: To evaluate the efficacy of ibrutinib compared to chlorambucil in the firstline treatment of CLL. Method: Systematic review of randomised clinical trials evaluating the efficacy of ibrutinib compared to chlorambucil in adult patients with previously untreated CLL. The MEDLINE, EMBASE, LILACS and Cochrane Library (CENTRAL) databases were searched, as well as grey literature databases such as Google Scholar, the CAPES thesis catalogue, the Brazilian Digital Library of Theses and Dissertations (BDTD), Open Access Theses and Dissertations, Mednar, World Wide Science and WorldCat. The Cochrane RoB 2 tool was used to assess the risk of bias and the GRADE tool was used to assess the certainty of the body of evidence. Results: The search resulted in the initial identification of 2,228 titles. After removing duplicates, 1,704 studies were submitted to title and abstract analysis. 2,373 records were assessed in grey literature databases, but none were included. From this analysis, seven articles progressed to full reading, six of which were excluded because they were conference abstracts or records of the same clinical trial. In the end, only the RESONATE-2 study met the eligibility criteria. The RESONATE-2 study was a phase III clinical trial that assessed the efficacy and safety of ibrutinib compared to chlorambucil as first-line treatment in patients with chronic lymphocytic leukaemia or small cell lymphocytic lymphoma. The results of the study showed that ibrutinib is superior to chlorambucil in terms of progression-free survival and overall survival. Conclusion: Chlorambucil is a drug with low representation in the current scientific literature, with lower efficacy and a higher incidence of adverse events compared to ibrutinib. The latter, a Bruton's tyrosine kinase inhibitor, stands out for its selectivity, better efficacy and a more favourable safety profile compared to chlorambucil. This makes it a therapeutic option in the initial treatment of CLL. Thus, given the apparent absence of a national guideline for this disease, there is favourable evidence of the drug's efficacy when compared to chlorambucil.
Introduction: Chronic lymphocytic leukaemia (CLL) is an indolent neoplasm characterised by the proliferation and accumulation of morphologically mature but immunologically dysfunctional B lymphocytes. It is the most common type of leukaemia in Western populations. The current scenario for the supply of oncological drugs by the SUS still faces challenges, despite recent advances. In the literature, the treatment of CLL is individualised and can include target therapies such as Bruton's tyrosine kinase (BTK) inhibitors, chemotherapy and haematopoietic stem cell transplantation. Ibrutinib is a BTK inhibitor registered in Brazil for the treatment of CLL. Chlorambucil is currently the most prescribed drug in Rio de Janeiro State Health Department units. Objective: To evaluate the efficacy of ibrutinib compared to chlorambucil in the firstline treatment of CLL. Method: Systematic review of randomised clinical trials evaluating the efficacy of ibrutinib compared to chlorambucil in adult patients with previously untreated CLL. The MEDLINE, EMBASE, LILACS and Cochrane Library (CENTRAL) databases were searched, as well as grey literature databases such as Google Scholar, the CAPES thesis catalogue, the Brazilian Digital Library of Theses and Dissertations (BDTD), Open Access Theses and Dissertations, Mednar, World Wide Science and WorldCat. The Cochrane RoB 2 tool was used to assess the risk of bias and the GRADE tool was used to assess the certainty of the body of evidence. Results: The search resulted in the initial identification of 2,228 titles. After removing duplicates, 1,704 studies were submitted to title and abstract analysis. 2,373 records were assessed in grey literature databases, but none were included. From this analysis, seven articles progressed to full reading, six of which were excluded because they were conference abstracts or records of the same clinical trial. In the end, only the RESONATE-2 study met the eligibility criteria. The RESONATE-2 study was a phase III clinical trial that assessed the efficacy and safety of ibrutinib compared to chlorambucil as first-line treatment in patients with chronic lymphocytic leukaemia or small cell lymphocytic lymphoma. The results of the study showed that ibrutinib is superior to chlorambucil in terms of progression-free survival and overall survival. Conclusion: Chlorambucil is a drug with low representation in the current scientific literature, with lower efficacy and a higher incidence of adverse events compared to ibrutinib. The latter, a Bruton's tyrosine kinase inhibitor, stands out for its selectivity, better efficacy and a more favourable safety profile compared to chlorambucil. This makes it a therapeutic option in the initial treatment of CLL. Thus, given the apparent absence of a national guideline for this disease, there is favourable evidence of the drug's efficacy when compared to chlorambucil.
Description
Palavras-chave
Leucemia Linfocítica Crônica de Células B, clorambucila, Ibrutinibe, Leukaemia, Lymphocytic, Chronic, B-Cell, Chlorambucil, Ibrutinib.
Citação
El Adji S. Revisão sistemática da eficácia do Ibrutinibe em comparação com a Clorambucila no tratamento de primeria linha da leucemia linfocítica crônica. Rio de janeiro. Dissertação[Mestrado Profissional em Avaliação de Tecnologias em Saúde] - Instituto Nacional de Cardiologia, 2025.