MULTIPLE MYELOMA AND OTHER PLASMA CELL DISEASES

multiplemyelomawos

NOVEL TREATMENT APPROACHES IN ADVANCED MYELOMA

Berrin Balık1 Hakan Göker2

1Gazi Yaşargil Training and Research Hospital, Department of Hematology, Diyarbakır, Türkiye
2Hacettepe University, Faculty of Medicine, Department of Hematology, Ankara, Türkiye

Balık B, Göker H. Novel Treatment Approaches in Advanced Myeloma. In: Sevindik ÖG, editor. Multiple Myeloma and Other Plasma Cell Dyscrasias. 1st ed. Ankara: Türkiye Klinikleri; 2025. p.79-92.

ABSTRACT

Enhanced comprehension of the functions of both the innate and adaptive immune systems in the development of cancers, such as multiple myeloma (MM), has resulted in the creation of innovative immune-based treatments. These cell-surface transmembrane proteins, which are expressed by plasma cells and have been identified as important immunotherapeutic targets in multiple myeloma (MM), include 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). Patients with heavily pretreated relapsed and/or refractory disease have shown encouraging activity with these treatments. Bispecific T cell engagers, autologous chimeric antigen receptor T cells that target BCMA or GPRC5D, and antibody–drug conjugates have all been authorized since 2020 for the treatment of relapsed and/ or refractory MM. Nevertheless, acquired resistance always happens, and not everyone responds to these treatments. Changes in cellular signaling pathways and clonal evolution are common ways for myeloma cells to become resistant to drugs. Thus, it is essential to keep looking for new targets in MM in order to avoid cumulative drug resistance, get past toxicities that limit treatment, and enhance outcomes in this incurable illness. We go over the different immunotherapeutic strategies that are either available or in clinical development for patients with MM in this review. These strategies target BCMA, GPRC5D, and FcRL5. Along with reviewing the mechanisms behind resistance to these therapies, we also talk about possible ways to get past them and enhance patient outcomes.

Keywords: Multiple myeloma; Adoptive immunotherapy; Immunogenetics

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