Diretrizes brasileiras de manejo de toxicidades imunomediadas associadas ao uso de bloqueadores de correceptores imunes

RESUMO

Nos últimos anos, assistimos à consolidação da “imunoterapia” como uma forma efetiva e viável de se tratar o câncer. Em particular, a manipulação terapêutica de moléculas envolvidas na modulação da resposta imune com o uso de anticorpos monoclonais, ou bloqueadores de correceptores imunes, viabilizou uma nova realidade para pacientes com melanoma, câncer de pulmão e diversas outras neoplasias. Como exemplos, bloqueadores do cytotoxic T lymphocyte associated antigen 4 (CTLA-4) e programmed cell death protein 1 (PD-1) foram recentemente incorporados à prática clínica após aprovações por agências reguladoras no Brasil e em inúmeros outros países, e novas modalidades e combinações para a mobilização do sistema imunológico estão em estudo. Todavia, essa ativação imune, particularmente de linfócitos T, leva ao risco do desenvolvimento de respostas direcionadas a tecidos sadios que se manifestam clinicamente como eventos adversos imunomediados. Nesse contexto, o conhecimento do perfil de segurança desses fármacos e dos passos para o tratamento eficaz desses eventos adversos é fundamental, e ganhará ainda mais importância nos próximos anos, frente ao crescimento de indicações dos bloqueadores de correceptores imunes, do número de pacientes tratados com esses agentes e à sua incorporação à prática da oncologia. Com esse foco, a presente diretriz se propõe a discutir o espectro de toxicidades relacionadas ao uso de bloqueadores de correceptores imunes e as estratégias destinadas a permitir o seu diagnóstico precoce e manejo adequado.

ABSTRACT

In the past few years, we have witnessed the consolidation of "immunotherapy" as an effective and viable way of treating cancer. Therapeutic intervention using monoclonal antibodies targeting molecules that modulate the immune response, or immune co-receptors, broadened the clinical benefit expectations for patients affected by melanoma, lung cancer and several other neoplasms. As an example, cytotoxic T-lymphocyte associated antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1) blockers have been recently incorporated into clinical practice after approvalby the regulatory agencies in several countries, including Brazil, and new combination modalities for the engagement of the immune system are currently being studied. Nonetheless, immune activation, especially of T-lymphocytes, carries the risk of triggering responses towards healthy tissues, which are manifested as immune-mediated adverse events. In this context, learning the safety profile of these drugs and the stepwise management of adverse events is crucial. Over the next years, a rise in indications is expected, and consequently, consistent incorporation into the oncological practice and an increase in the number of treated patients are likely to occur. Therefore, the purpose of this guideline is to discuss the range of toxicities related to the use of immune co-receptor blockers and the strategies that allow their early diagnosis and proper management.

Descritores:

Imunoterapia - Antígeno CTLA-4 - Receptor de morte celular programada 1 - An-ticorpos monoclonais

Keywords:

Immunotherapy - CTLA-4 antigen - Programmed cell death 1 receptor - Antibodies, monoclonal

Publication History

Received: 27 February 2017

Accepted: 14 March 2017

Article published online:
07 March 2025

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