Dr Ikegawa on An Analysis of Rapidly Manufactured Durcabtagene Autoleucel in R/R Multiple Myeloma

The trial utilized the T-Charge platform to produce BCMA-targeted CAR T-cells within less than 2 days. Notably, this manufacturing period is much shorter than the conventional CAR T-cell manufacturing process, which may induce or bolster T-cell proliferation and functioning. The trial included patients with heavily pretreated, relapsed/refractory multiple myeloma who were previously exposed to at least 2 lines of prior therapy. At a data cutoff of March 28, 2023, 31 patients had enrolled onto the dose-expansion portion of the trial and received doses ranging from 2.5 × 106 to 20 × 106 T cells. A correlative analysis was subsequently performed in this patient population.

Findings from this analysis were reported at the 2023 IMS Annual Meeting and revealed the efficacy of the CAR T-cell therapy in achieving rapid and robust in vivo expansion, along with sustained T-cell presence in individuals with relapsed/refractory multiple myeloma, Ikegawa reports. Nearly all patients exhibited a positive response, with only 1 patient who received the lowest dose level not responding to treatment. This resulted in an overall response rate of 97%, encompassing a stringent complete response rate of 38.7%, a very good partial response rate of 38.7%, and a partial response rate of 19.4%.

Further analysis of CAR T-cell kinetics using fresh blood samples from all patients via flow cytometry was performed, he continues. Additionally, investigators analyzed samples from apheresis, the final CAR T-cell product, and post-infusion peripheral blood mononuclear cells using mass cytometry and T-cell sequencing for the initial 15 patients. At all dose levels, robust CAR T-cell expansion was observed, with peak expansion occurring on day 14. Notably, at the time of peak expansion, a majority of patients exhibited CAR T cells constituting over 50% of the circulating T cells in their bloodstream.

Ongoing monitoring of patients revealed sustained high levels of circulating T cells in the peripheral blood at the 1-year mark or later post-CAR T-cell infusion, Ikegawa adds. The expansion of CAR T cells was associated with an increase in inflammatory cytokines, consistent with previous reports on CAR T-cell expansion. Researchers also observed a correlation between longer CAR T-cell persistence and lower levels of soluble BCMA in a subset of patients, indicating the preservation of functional activity against BCMA over an extended period.

Analyses of apheresis samples vs the final CAR T-cell product demonstrated an increase in CD3 stem-like memory T cells (Tscm) and a decrease in CD3-naïve T cells during the manufacturing process., Ikegawa details. Furthermore, T-cell diversity comparisons between Tscm cells and memory cells in the final CAR T-cell product indicated greater heterogeneity in Tscm cells for both CD4 and CD8. Notably, post-infusion CAR-positive T cells exhibited a closer resemblance to the Tscm repertoire than to memory T cells in the produced CAR T-cells, suggesting their origin from Tscm cells within the CAR T cell products, he concludes.