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Terapias biológicas no tratamento da leucemia linfoblástica aguda : eficácia e segurança
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A leucemia linfoblástica aguda é uma neoplasia hematológica caracterizada pela proliferação de células linfoides imaturas na medula óssea, sangue periférico e outros órgãos. Atualmente é o cancro mais comum em doentes pediátricos e apresenta taxas de sobrevivência de 90% em crianças e 40% em adultos com mais de 40 anos.
Um diagnóstico completo da leucemia linfoblástica aguda inclui uma avaliação molecular e citogenética e imunofenotipagem bem como, a avaliação dos sinais e sintomas do doente. É necessária a presença de pelo menos 20% de linfoblastos na medula óssea e sangue periférico como critério para distinguir leucemia linfoblástica aguda de linfoma linfoblástico.
A terapia convencional para a leucemia linfoblástica aguda inclui protocolos intensivos de quimioterapia divididos em várias etapas: indução, profilaxia do sistema nervoso central, consolidação e manutenção. Alguns doentes acabam por prosseguir para transplante de células tronco hematopoiéticas. No entanto, esta terapia apresenta toxicidades elevadas, surgindo a necessidade da criação de novas terapias direcionadas com perfis de toxicidade mais baixos. Surge assim a terapia direcionada, esta inclui os inibidores da tirosina-cinase e as terapias biológicas, incluindo estas anticorpos monoclonais, anticorpos monoclonais conjugados com agentes citotóxicos ou toxinas, anticorpos biespecíficos e terapias com células T recetoras de antigénios quiméricos.
Os inibidores da tirosina-cinase são fármacos que têm como principal alvo a leucemia linfoblástica aguda Ph+. Os anticorpos monoclonais abordados ao longo deste trabalho têm como principal alvo CD19, CD3, CD20 e CD22 e são maioritariamente eficazes em leucemia linfoblástica aguda das células B.
Têm sido realizados diversos ensaios clínicos que avaliam a eficácia destas terapias tanto em monoterapia, como em combinação com agentes presentes em quimioterapia convencional, como em combinação com outras terapias direcionadas, e os resultados têm-se apresentado bastante promissores. Estas terapias, devido ao facto de serem direcionadas para o alvo apresentam melhores perfis de toxicidade em comparação com as terapias tradicionais.
A continuação da realização de investigação nesta área é fundamental tal como a realização de novos ensaios clínicos de forma a avaliar a eficácia e segurança destas terapias a longo prazo.
Acute lymphoblastic leukemia is an hematological malignancy characterized by the proliferation of immature lymphoid cells in the bone marrow, peripheral blood and other organs. It is currently the most common cancer in pediatric patients and has survival rates of 90% in children and 40% in adults over 40 years of age. A complete diagnostic evaluation of acute lymphoblastic leukemia includes molecular and cytogenetic evaluation and immunophenotyping as well as an assessment of the patient's signs and symptoms. The presence of at least 20% lymphoblasts in the bone marrow and peripheral blood is required as a criteria to distinguish acute lymphoblastic leukemia from lymphoblastic lymphoma. Conventional therapy for acute lymphoblastic leukemia includes intensive chemotherapy protocols divided into several stages: induction, central nervous system prophylaxis, consolidation, and maintenance. Some patients end up needing hematopoietic stem cell transplantation. However, this therapy carries high toxicities, resulting in the need to create new targeted therapies with lower toxicity profiles. Targeted therapy includes tyrosine kinase inhibitors and biological therapies, these being monoclonal antibodies, monoclonal antibodies conjugated with cytotoxic agents or toxins, bispecific antibodies, and therapies with chimeric antigen T cell receptors. Tyrosine kinase inhibitors are drugs whose main target is Ph+ acute lymphoblastic leukemia. The monoclonal antibodies discussed throughout this essay have CD19, CD3, CD20 and CD22 as their main target and are mostly effective in B-cell acute lymphoblastic leukemia. Several clinical trials have been carried out to evaluate the effectiveness of these therapies both in monotherapy and in combination with agents present in conventional chemotherapy, as well as in combination with other targeted therapies, and the results have been very promising. Due to the fact that they are targeted, these therapies have better toxicity profiles compared with traditional therapies. It is fundamental to carry out research in this area, as well as carrying out new clinical trials in order to evaluate the long-term efficacy and safety of these therapies.
Acute lymphoblastic leukemia is an hematological malignancy characterized by the proliferation of immature lymphoid cells in the bone marrow, peripheral blood and other organs. It is currently the most common cancer in pediatric patients and has survival rates of 90% in children and 40% in adults over 40 years of age. A complete diagnostic evaluation of acute lymphoblastic leukemia includes molecular and cytogenetic evaluation and immunophenotyping as well as an assessment of the patient's signs and symptoms. The presence of at least 20% lymphoblasts in the bone marrow and peripheral blood is required as a criteria to distinguish acute lymphoblastic leukemia from lymphoblastic lymphoma. Conventional therapy for acute lymphoblastic leukemia includes intensive chemotherapy protocols divided into several stages: induction, central nervous system prophylaxis, consolidation, and maintenance. Some patients end up needing hematopoietic stem cell transplantation. However, this therapy carries high toxicities, resulting in the need to create new targeted therapies with lower toxicity profiles. Targeted therapy includes tyrosine kinase inhibitors and biological therapies, these being monoclonal antibodies, monoclonal antibodies conjugated with cytotoxic agents or toxins, bispecific antibodies, and therapies with chimeric antigen T cell receptors. Tyrosine kinase inhibitors are drugs whose main target is Ph+ acute lymphoblastic leukemia. The monoclonal antibodies discussed throughout this essay have CD19, CD3, CD20 and CD22 as their main target and are mostly effective in B-cell acute lymphoblastic leukemia. Several clinical trials have been carried out to evaluate the effectiveness of these therapies both in monotherapy and in combination with agents present in conventional chemotherapy, as well as in combination with other targeted therapies, and the results have been very promising. Due to the fact that they are targeted, these therapies have better toxicity profiles compared with traditional therapies. It is fundamental to carry out research in this area, as well as carrying out new clinical trials in order to evaluate the long-term efficacy and safety of these therapies.
Descrição
Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, 2023, Universidade de Lisboa, Faculdade de Farmácia.
Palavras-chave
Leucemia linfoblástica aguda Terapias biológicas Inibidores da tirosinacinase Anticorpos monoclonais Células CAR-T Mestrado Integrado - 2023