Toxicity Profile of Chimeric Antigen Receptor T-Cell and Bispecific Antibody Therapies in Multiple Myeloma: Pathogenesis, Prevention and Management

Abstract

Multiple myeloma is the second-most common hematologic malignancy in adults worldwide. Despite ongoing advancement in therapeutic modalities, it remains an incurable disease with a 5-year survival rate of approximately 50%. The recent development and introduction of anti-BCMA immunotherapies into clinical practice, including chimeric antigen receptor T-cell (CAR-T) therapies and bispecific antibodies, has radically shifted the treatment paradigm. However, despite the promising potential of these therapies for broader application, frequent and significant adverse effects have been reported, both in short- and in long-term settings, requiring increasing awareness and vigilance in the treating team, close monitoring, and prompt interventions with a multidisciplinary approach. In this review, we will discuss the toxicities associated with CAR-T cell and bispecific antibody therapies, focusing on results from major clinical studies and real-world observations. In addition, we will emphasize on effective strategies for prevention, monitoring and management, and provide expert recommendations.

Keywords: CAR T-cell therapy; bispecific antibodies; cytokine release syndrome; hematotoxicity; infections; neurotoxicity.

Figure 1

Pathophysiology of Cytokine Release Syndrome (CRS) and Immune Cell–associated Neurologic Syndrome. (ICANS). Abbreviation: CAR, chimeric antigen receptor; IFN-γ, interferon-γ; TNF, tumor necrosis factor; NOS, nitric oxide; GM-CSF, granulocyte–macrophage colony-stimulating factor; NK, natural killer; DC, dendritic cells; MIP, macrophage inflammatory protein; MCP-1, monocyte chemoattractant protein-1; CNS, central nervous system.