Dr Spencer on Differentiating Factors for In Vivo CAR T-Cell Therapy in Myeloma

The whole logistical side of [CAR T-cell therapy] is sort of removed [with KLN-1010]. The challenges are removed, so the real question now is [about] the deliverability, safety, and the durability of responses.

Andrew Spencer, MBBS, FRACP, FRCPA, DM, a professor of hematology at Monash University and head of the Malignant Haematology, Transplantation, and Cellular Therapy Service and the Myeloma Research Group at The Alfred Hospital, discussed what separates in vivo CAR T-cell therapy from conventional autologous CAR T-cell therapy in the treatment of patients with relapsed/refractory multiple myeloma.

At the 2026 EHA Congress, Spencer presented data from the phase 1 inMMyCAR trial (NCT07075185), which is evaluating the in vivo CAR T-cell therapy KLN-1010 in patients with relapsed/refractory myeloma. Findings showed that all evaluable patients (n = 18) experienced an overall response, including 22% who had a stringent complete response and 6% who had a complete response. Futhermore, minimal residual disease–negative bone marrow responses at a 10^–5 sensitivity occurred in all evaluable patients (n = 14).

Spencer explained that currently approved BCMA-directed autologous CAR T-cell therapies require leukapheresis, ex vivo manufacturing, lymphodepleting chemotherapy, and a manufacturing interval that can extend several weeks. Conversely, the investigational in vivo approach generates BCMA-directed CAR T cells directly within the patient. Spencer explained that this paradigm eliminates the need for cell collection and centralized manufacturing, potentially allowing treatment to be initiated within days rather than the weeks required for autologous CAR T-cell therapy.

According to Spencer, shortening the treatment timeline could have important clinical implications, as many patients with relapsed/refractory multiple myeloma experience disease progression during the wait for CAR T-cell manufacturing, preventing them from receiving their planned infusion. By removing these logistical obstacles, in vivo CAR T-cell therapy may improve treatment accessibility and reduce attrition between treatment referral and administration.

Although the simplified delivery process represents a major potential advantage, Spencer emphasized that key clinical questions remain. Ongoing studies will need to establish whether in vivo CAR T-cell therapy can consistently generate effective BCMA-targeted immune responses, as well as demonstrate an acceptable safety profile and durable clinical benefit. As clinical development continues, these efficacy and safety data will determine whether this novel platform can serve as a practical alternative to traditional autologous CAR T-cell therapy in multiple myeloma, he said.