Bispecific Antibodies vs CAR T-Cells: Mechanistic and Practical Distinctions

This segment explores a foundational question in modern myeloma care: how do BCMA-directed bispecific antibodies differ from BCMA-targeted CAR T-cell therapy? Nisha Joseph, MD, leads the explanation, emphasizing that, although both modalities harness T-cell–mediated cytotoxicity, their mechanisms and logistics diverge significantly. Bispecific antibodies function as off-the-shelf T-cell engagers, binding simultaneously to CD3 on endogenous T cells and BCMA on plasma cells, thereby redirecting the patient’s circulating T cells toward tumor killing. Their availability allows treatment initiation within days, which is an invaluable advantage for patients with rapidly progressive disease.

CAR T-cell therapy, by contrast, involves collecting the patient’s T cells, genetically modifying them ex vivo to express a BCMA-targeted receptor, expanding them, and reinfusing them after lymphodepletion. Joseph notes that this manufacturing process requires 2 to 4 weeks or longer, introducing delays that can be prohibitive for unstable patients. Additionally, CAR T cells undergo in-vivo expansion that clinicians cannot control, resulting in a different toxicity profile, including more severe cytokine release syndrome (CRS) and neurotoxicity.

Jagannath underscores the clinical implications: bispecific antibodies can be repeatedly administered, titrated, held, or discontinued as needed, giving clinicians greater control over dosing and toxicity management. CAR T, once infused, follows its own biological trajectory. The panel collectively highlights that both approaches have unique strengths, and understanding these distinctions helps clinicians tailor therapy based on disease tempo, patient fitness, and urgency for disease control. The segment concludes with agreement that although CAR T remains an invaluable option, bispecific antibodies fill a critical niche, particularly for patients who require immediate, flexible, immune-redirecting treatment.