Fractionated BCMA-Directed CAR T-Cell Therapy ARI0002h Demonstrates Encouraging Responses Among Patients With R/R Multiple Myeloma

Interim Analysis from the CARTBCMA-HCB-01 Single-Arm Multicenter Pilot Study

An interim analysis from the CARTBCMA-HCB-01 pilot study demonstrated that ARI0002h, a B-cell maturation antigen (BCMA)-targeted chimeric antigen receptor (CAR) T-cell therapy developed within the academic setting, demonstrated encouraging responses when administered in a fractionated manner with a booster dose after 3 months to patients with relapsed/refractory (R/R) multiple myeloma (MM). 

Aina Oliver-Caldés, MD, University of Barcelona, Barcelona, Spain, and coauthors sought to evaluate the efficacy and safety of ARI0002h among patients with R/R MM in this single-arm, multicenter academic pilot study. The primary end points included the overall response rate 100 days post-first infusion and the incidence of cytokine-release syndrome or neurotoxic events within the first 30 days following treatment. 

A total of 35 eligible patients with R/R MM who had an Eastern Cooperative Oncology Group performance status of 0 to 2 and had undergone at least 2 prior lines of therapy (including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody) were enrolled in this study. Additionally, all patients were refractory to their last line of therapy and had measurable disease according to the International Myeloma Working Group. Of the enrolled patients, 86% (n = 30) received ARI0002h. 

Patients received an initial fractionated infusion of 3 × 106 CAR T-cells per kg body weight, administered in 3 aliquots. They also received a non-fractionated booster dose of up to 3 × 106 CAR T-cells per kg body weight, administered at least 100 days post-first infusion. 
At the data cutoff, the overall response rate during the first 100 days from infusion was 100%. Notably, 80% (n = 24) of the 30 patients achieved a very good partial response or better, with 50% (n = 15) achieving a complete response, 30% (n = 9) achieving a very good partial response and 20% (n = 6) reaching partial response. 

Cytokine-release syndrome, primarily of grades 1 to 2 in severity, was seen in 80% (n = 24) of patients. No neurotoxic events were observed. The study authors noted that persistent grade 3 to 4 cytopenias and infections were observed in 67% (n = 20) of patients. They reported 3 patient fatalities, due to disease progression, head injury, and COVID-19. 

As end points were met, the study authors concluded, “ARI0002h administered in a fractioned manner with a booster dose after 3 months can provide deep and sustained responses in patients with relapsed or refractory multiple myeloma, with a low toxicity, especially in terms of neurological events, and with the possibility of a point-of-care approach.” 

Source: 

Oliver-Caldés A, González-Calle V, Cabañas V, et al. Fractionated initial infusion and booster dose of ARI0002h, a humanised, BCMA-directed CAR T-cell therapy, for patients with relapsed or refractory multiple myeloma (CARTBCMA-HCB-01): a single-arm, multicentre, academic pilot study. Lancet Oncol. Published online: July 3, 2023. doi: 10.1016/S1470-2045(23)00222-X