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Mieloma múltiplo: fisiopatologia e abordagem terapêutica
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Introdução: O mieloma múltiplo é uma neoplasia maligna, caracterizada pela proliferação descontrolada dos plasmócitos. É um distúrbio com grande relevância clínica dentro das alterações hematológicas malignas e continua incurável. A inibição da apoptose das células cancerígenas e a libertação de citocinas são fatores preponderantes no desenvolvimento da doença. São vários os fatores envolvidos na sua fisiopatologia, nomeadamente: fatores de crescimento; fatores que promovem o desequilíbrio entre a formação e a reabsorção do osso; anomalias genéticas; desregulação epigenética e das células estaminais mesenquimais. O tratamento destes doentes engloba terapêutica farmacológica e cuidados de suporte. A terapia farmacológica é distinta consoante os doentes são ou não elegíveis para transplante autólogo de células estaminais e engloba quimioterápicos clássicos (melfalano e vincristina), corticosteróides (prednisona) e terapia biológica (bortezomib e lenalidomida).
Objetivo: Enumerar e descrever, através de revisão sistemática, as abordagens terapêuticas utilizadas e emergentes com base no conhecimento, cada vez mais aprofundado, da fisiopatologia heterogénea da doença.
Materiais e Métodos: Revisão bibliográfica através da utilização da base de dados PUBMED.
Resultados: A adição de talidomida ao tratamento tido como padrão, melfalano-prednisona, aumentou em 20% a sobrevida livre de progressão da doença. Surgiram como efeitos adversos a neuropatia periférica e os eventos trombóticos.
Discussão: A introdução de novos agentes terapêuticos, nomeadamente de imunomoduladores, como a lenalidomida e inibidores de proteossoma, como o bortezomib aumentaram significativamente as taxas de remissão da doença e a incidência de efeitos adversos foi reversível com a diminuição ou suspensão da dose.
Conclusão: Os avanços terapêuticos, o conhecimento da fisiopatologia e um diagnóstico cada vez mais precoce revelam benefícios inegáveis e que são refletidos no alcance de uma sobrevida de 10 anos.
Introduction: Multiple myeloma is a malignant neoplasm, characterized by uncontrolled proliferation of the plasma cells. It is a disorder of great clinical relevance within malignant hematological disorders and remains incurable. Inhibition of cancer cell apoptosis and release of cytokines are major factors in the development of the disease. There are several factors involved in its pathophysiology, specifically: growth factors; factors that promote imbalance between bone formation and bone resorption; genetic anomalies; epigenetic and mesenchymal stem cells deregulation. Treatment of these patients encompasses pharmacological therapy and supportive care. Pharmacological therapy is distinct according to whether or not patients are eligible for autologous stem cell transplantation and consists of classical chemotherapy (melphalan and vincristine), corticosteroids (prednisone) and biological therapy (bortezomib and lenalidomide). Objective: To list and describe, through a systematic review, the therapeutic approaches already in use and emerging based on the increasing knowledge of the heterogeneous pathophysiology of the disease. Methods: Bibliographic review using the PUBMED database. Results: The addition of thalidomide to the standard treatment, melphalan-prednisone, increased the progression-free survival of patients by 20%. Peripheral neuropathy and thrombotic events have appeared as adverse effects. Discussion: The introduction of new therapeutic agents, namely immunomodulators such as lenalidomide and proteasome inhibitors such as bortezomib, significantly increased remission rates of the disease and the incidence of adverse events was reversible with dose reduction or suspension. Conclusion: Therapeutic advances, knowledge of pathophysiology and an increasingly early diagnosis reveal undeniable benefits and are reflected in the achievement of a 10-years survival.
Introduction: Multiple myeloma is a malignant neoplasm, characterized by uncontrolled proliferation of the plasma cells. It is a disorder of great clinical relevance within malignant hematological disorders and remains incurable. Inhibition of cancer cell apoptosis and release of cytokines are major factors in the development of the disease. There are several factors involved in its pathophysiology, specifically: growth factors; factors that promote imbalance between bone formation and bone resorption; genetic anomalies; epigenetic and mesenchymal stem cells deregulation. Treatment of these patients encompasses pharmacological therapy and supportive care. Pharmacological therapy is distinct according to whether or not patients are eligible for autologous stem cell transplantation and consists of classical chemotherapy (melphalan and vincristine), corticosteroids (prednisone) and biological therapy (bortezomib and lenalidomide). Objective: To list and describe, through a systematic review, the therapeutic approaches already in use and emerging based on the increasing knowledge of the heterogeneous pathophysiology of the disease. Methods: Bibliographic review using the PUBMED database. Results: The addition of thalidomide to the standard treatment, melphalan-prednisone, increased the progression-free survival of patients by 20%. Peripheral neuropathy and thrombotic events have appeared as adverse effects. Discussion: The introduction of new therapeutic agents, namely immunomodulators such as lenalidomide and proteasome inhibitors such as bortezomib, significantly increased remission rates of the disease and the incidence of adverse events was reversible with dose reduction or suspension. Conclusion: Therapeutic advances, knowledge of pathophysiology and an increasingly early diagnosis reveal undeniable benefits and are reflected in the achievement of a 10-years survival.
Descrição
Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, Universidade de Lisboa, Faculdade de Farmácia, 2017
Palavras-chave
Mieloma múltiplo Fisiopatologia Abordagem terapêutica Mestrado Integrado - 2017