Exploring CAR T-Cell Therapy Efficacy in Earlier Vs Later Lines of Therapy

EP: 1.iMMagine-1: Anito-Cel Shows Efficacy in R/R Multiple Myeloma

EP: 2.Safety and Outpatient Potential of Anito-Cel in Multiple Myeloma

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EP: 3.Exploring CAR T-Cell Therapy Efficacy in Earlier Vs Later Lines of Therapy

EP: 4.Linking T-Cell Composition to CAR T Efficacy in Multiple Myeloma

This interview discusses translational and clinical insights from data presented at ASH 2025, with a focus on why earlier-line use of CAR T-cell therapy leads to improved outcomes in multiple myeloma. The conversation emphasizes that while logistical advantages of earlier CAR T use have long been recognized, emerging biologic data now provide a clearer explanation for the observed differences in efficacy.

From a practical standpoint, administering CAR T-cell therapy earlier in the disease course is more feasible. Patients are generally fitter, have less aggressive or refractory disease, and have access to more effective and tolerable bridging therapy options. As a result, more patients can successfully reach CAR T infusion in earlier lines compared with later lines, where rapid progression and cumulative toxicity often interfere with treatment delivery.

Beyond logistics, the interview highlights compelling translational data showing that T-cell quality differs substantially depending on prior treatment exposure. Patients who have received multiple prior lines of therapy—often including prolonged steroid use, proteasome inhibitors, IMiDs, and anti-CD38 antibodies—tend to have more exhausted, dysfunctional T cells. This exhausted phenotype likely contributes to inferior CAR T expansion, persistence, and ultimately progression-free survival in later-line settings. In contrast, earlier-line patients typically have more robust and functional T cells, which may explain the superior outcomes seen with cilta-cel when used earlier.

The discussion also explores the concept of immune fitness declining through approximately 3 prior lines of therapy before reaching a plateau. Continuous therapy over years can progressively impair endogenous immunity, particularly in patients with high-risk disease who relapse quickly and require repeated treatments. By the time patients reach three lines of therapy, cumulative immune damage is evident, including reductions in effector T cells and possible increases in regulatory populations. However, earlier intervention—before this immune decline becomes pronounced—appears to preserve T-cell function and maximize CAR T efficacy.

Overall, these findings reinforce the importance of considering cilta-cel earlier in the treatment paradigm, not only to improve access and feasibility but also to capitalize on a more intact immune system that can support durable CAR T-cell responses.