Just scratching the surface: novel treatment approaches for multiple myeloma targeting cell membrane proteins
Cet article examine les différentes approches immunothérapeutiques ciblant l'antigène de maturation des lymphocytes B, la protéine GPRC5B ou la protéine FcRL5 chez les patients atteints d'un myélome multiple, passe en revue les mécanismes de résistance à ces traitements puis identifie des stratégies potentielles pour contrecarrer ces mécanismes et améliorer les résultats thérapeutiques
A better understanding of the roles of the adaptive and innate immune systems in the oncogenesis of cancers including multiple myeloma (MM) has led to the development of novel immune-based therapies. B cell maturation antigen (BCMA), G protein-coupled receptor family C group 5 member D (GPRC5D) and Fc receptor-like protein 5 (FcRL5, also known as FcRH5) are cell-surface transmembrane proteins expressed by plasma cells, and have been identified as prominent immunotherapeutic targets in MM, with promising activity demonstrated in patients with heavily pretreated relapsed and/or refractory disease. Indeed, since 2020, antibody–drug conjugates, bispecific T cell engagers and autologous chimeric antigen receptor T cells targeting BCMA or GPRC5D have been approved for the treatment of relapsed and/or refractory MM. However, responses to these therapies are not universal, and acquired resistance invariably occurs. In this Review, we discuss the various immunotherapeutic approaches targeting BCMA, GPRC5D and FcRL5 that are currently either available or in clinical development for patients with MM. We also review the mechanisms underlying resistance to such therapies, and discuss potential strategies to overcome these mechanisms and improve patient outcomes.
Nature Reviews Clinical Oncology , résumé, 2024