Sequencing CAR T-Cell Therapy in the Evolving Myeloma Treatment Landscape

This interview discusses how BCMA-directed CAR T-cell therapy in multiple myeloma may be more effective when administered earlier in the treatment sequence, also highlighting safety considerations, particularly immune effector cell-associated enterocolitis (IEC).

The discussion emphasizes that patients receiving ciltacabtagene autoleucel (cilta-cel) therapy earlier—such as in second or third line rather than later lines—tend to have superior progression-free survival (PFS). This improvement is attributed to 2 main factors: the disease is less treatment-resistant earlier in its course, and patients’ T cells are less exhausted, which supports better CAR T-cell expansion, persistence, and ultimately deeper, more durable responses. Early-line administration also offers the potential for longer treatment-free intervals, and investigators hope that longer follow-up may reveal higher proportions of patients achieving long-term remission or even cure-like outcomes.

The interview also addresses the balance between efficacy and toxicity, particularly in light of the recent boxed warning for IEC. While CAR T-cell therapy offers remarkable response rates and treatment-free survival, serious toxicities remain a concern. Cytokine release syndrome (CRS) is generally manageable, but rare neurotoxicities, including Parkinsonian symptoms, and IEC-related enterocolitis can result in significant morbidity and mortality. Recent advances in earlier diagnosis and intervention have reduced mortality, but complete prevention remains an unmet need. Clinicians continue to weigh these risks when deciding whether to administer CAR T in second, third, or later lines, taking into account individual patient factors, tumor burden, and bridging therapy options.

Overall, findings presented at ASH 2025 strengthen the argument for earlier use of BCMA CAR T-cell therapy in multiple myeloma by demonstrating superior efficacy in less heavily treated patients with more functional T cells, while ongoing research aims to further mitigate rare but serious toxicities. This data underscores the evolving risk-benefit calculus that guides clinical decision-making in the CAR T era.