American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists · 2026
Therapy update: An introduction to the pharmacology, safety, and efficacy of bispecific antibodies in relapsed or refractory multiple myeloma.
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Ellayan Dawud
Аннотация
PURPOSE: The treatment landscape for relapsed or refractory multiple myeloma (RRMM) has evolved significantly with the introduction of T cell-redirecting therapies. This review details key pharmacology, clinical efficacy, and safety information for bispecific antibodies (bsAbs) approved or under investigation for RRMM.
SUMMARY: Multiple myeloma eventually relapses in nearly all patients, necessitating the continuous development of novel therapeutics. The 3 main targets for bsAbs on multiple myeloma cells are B cell maturation antigen (BCMA), G-protein-coupled receptor family C group 5 member D (GPRC5D), and Fc receptor homolog 5 (FcRH5). Clinical trials have demonstrated robust single-agent efficacy in patient populations with difficult-to-treat RRMM, including in patients with penta-refractory disease. However, these therapies are associated with unique toxicities, including cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, as well as significant infection risks. Risk can be reduced through close monitoring, optimized premedication regimens, and step-up dosing strategies.
CONCLUSION: The remarkable efficacy of bsAbs in RRMM combined with a maturing understanding of their toxicity profiles is fundamentally reshaping the RRMM treatment landscape.
SUMMARY: Multiple myeloma eventually relapses in nearly all patients, necessitating the continuous development of novel therapeutics. The 3 main targets for bsAbs on multiple myeloma cells are B cell maturation antigen (BCMA), G-protein-coupled receptor family C group 5 member D (GPRC5D), and Fc receptor homolog 5 (FcRH5). Clinical trials have demonstrated robust single-agent efficacy in patient populations with difficult-to-treat RRMM, including in patients with penta-refractory disease. However, these therapies are associated with unique toxicities, including cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, as well as significant infection risks. Risk can be reduced through close monitoring, optimized premedication regimens, and step-up dosing strategies.
CONCLUSION: The remarkable efficacy of bsAbs in RRMM combined with a maturing understanding of their toxicity profiles is fundamentally reshaping the RRMM treatment landscape.