Early Data Show Feasibility of in Vivo CAR T Therapy in Multiple Myeloma

This interview discusses early phase 1 findings from the inMMyCAR study presented at ASH 2025 evaluating KLN-1010, an investigational off-the-shelf, in vivo CAR T-cell approach in multiple myeloma, highlighting its potential to fundamentally change how CAR T therapy is delivered. Although the data are currently limited to only a small number of patients, the concept has generated significant excitement due to its ability to address many of the logistical and clinical barriers associated with traditional, ex vivo CAR T-cell therapy.

Conventional CAR T treatment requires T cell collection, complex manufacturing, bridging therapy to control disease during production, lymphodepleting chemotherapy, and careful coordination of timing—all of which can introduce delays, toxicity, and risk of failure. In contrast, in vivo CAR T involves direct administration of a viral vector that programs a patient’s own T cells inside the body to express the CAR construct. Early signals suggest that this process can generate meaningful T-cell expansion and clinical responses without the need for lymphodepletion chemotherapy.

If validated in larger studies, this approach could substantially reduce time to treatment, eliminate the need for bridging therapy, and lower overall toxicity and cost. Avoiding lymphodepletion alone may significantly improve tolerability, especially for frail or heavily pretreated patients. The observed T-cell expansion without chemotherapy also challenges long-standing assumptions about the necessity of lymphodepletion for CAR T efficacy and opens new avenues for understanding immune dynamics in myeloma.

Despite the enthusiasm, the interview emphasizes the need for caution. Key questions remain regarding durability of response, reproducibility across a broader patient population, and potential toxicities associated with systemic delivery of the CAR-encoding vector. Additionally, baseline immune fitness may play a critical role, as patients with more robust T-cell populations may respond differently than those with advanced immune exhaustion.

Overall, these early findings suggest that in vivo CAR T therapy is feasible and potentially transformative in multiple myeloma, while underscoring the importance of continued investigation to define patient selection, safety, and long-term outcomes before this approach can be integrated into routine clinical practice.