Determinants of Efficacy and Optimization of Chimeric Antigen Receptor T-Cell Therapy for Treating Multiple Myeloma: Current Status and Future Perspectives - PubMed
6 hours ago
- #CAR T-cell therapy
- #BCMA
- #Multiple Myeloma
- CAR T-cell therapy has revolutionized treatment for relapsed and refractory multiple myeloma (MM), especially with BCMA-directed products.
- Variability in response durability, treatment-related toxicities, and resistance highlight the need for strategies beyond CAR construct design.
- Therapeutic outcomes depend on tumor burden, antigen dynamics, CAR T-cell fitness, and host immune context at infusion.
- Effector-to-target balance and antigen load are key modifiable determinants of efficacy and safety.
- Pre-infusion disease control and response to bridging therapy significantly impact CAR T-cell expansion, persistence, and clinical outcomes.
- Soluble BCMA (sBCMA) is emerging as a biomarker for optimizing treatment timing and patient selection.
- Intrinsic properties of CAR T-cell products, like spatial organization of CAR molecules, influence treatment responses.
- Quantitative functional assessment of CAR T-cell products may improve prediction of therapeutic potency before infusion.
- The review discusses resistance mechanisms, pre-infusion disease control optimization, biomarkers, and emerging combination strategies.
- A patient-centered framework integrating CAR engineering with disease biology and host factors is proposed to enhance therapy consistency and safety.