Dr Spencer on the Potential Role for In Vivo CAR T-Cell Therapy in Myeloma

[In vivo CAR T-cell therapy] could be a real boon if it proves to be durable and is brought up earlier in the treatment algorithm.

Andrew Spencer, MBBS, FRACP, FRCPA, DM, a professor of hematology at Monash University and head of the Malignant Hematology, Transplantation, and Cellular Therapy Service and the Myeloma Research Group at The Alfred Hospital, discussed the potential role for in vivo CAR T-cell therapy and how this modality may affect the multiple myeloma treatment paradigm.

At the 2026 EHA Congress, Spencer and colleagues presented data from the phase 1 inMMyCAR trial (NCT07075185) evaluating the in vivo CAR T-cell therapy KLN-1010 in patients with relapsed or refractory multiple myeloma. Findings showed that evaluable patients (n = 18) experienced an overall response rate of 100%, including a stringent complete response (sCR) rate of 22%, a CR rate of 6%, a very good partial response (VGPR) rate of 22%, and a PR rate of 50%. All 14 patients evaluable for minimal residual disease (MRD) were MRD negative at a 10^-5 sensitivity.

Spencer noted that multiple myeloma is a biologically heterogeneous disease, despite the fact that many patients currently receive similar treatment approaches. He suggested that more individualized therapeutic strategies may ultimately improve patient outcomes, and he explained that in vivo CAR T-cell therapy could play an important role if ongoing clinical development continues to demonstrate favorable results.

Spencer noted that, if durable efficacy is confirmed, in vivo CAR T-cell therapy has the potential to replace conventional autologous CAR T-cell therapy. In vivo approaches could simplify treatment by generating CAR T cells directly within the patient, potentially overcoming some of the logistical challenges associated with manufacturing autologous cellular therapies, Spencer explained. He added that the greatest clinical impact may be realized if the therapy can be moved earlier in the treatment algorithm, rather than being reserved for patients with relapsed or refractory disease.

However, Spencer emphasized that broader implementation will depend on establishing an acceptable safety profile and identifying the patients most likely to benefit. He suggested that patients with standard-risk disease who achieve durable disease control with currently available therapies may not require a more intensive approach, whereas patients with higher-risk disease or those less likely to experience prolonged remissions could derive greater benefit from earlier use of in vivo CAR T-cell therapy.