In an interim analysis of a Spanish pilot trial (CARTBCMA-HCB-01) reported in The Lancet Oncology, Oliver-Caldés et al found that an academically developed B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T-cell therapy, ARI0002h, showed activity in patients with relapsed or refractory multiple myeloma.
Study Details
In the multicenter trial, 30 (86%) of 35 patients (33 underwent leukapheresis) enrolled between June 2020 and February 2021 who had received two or more previous lines of therapy including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody received ARI0002h. Patients received an initial fractionated infusion of 3 × 10⁶ CAR T cells/ kg in 3 aliquots (0.3, 0.9, and 1.8 × 10⁶ CAR-positive cells/kg on days 0, 3, and 7) and a nonfractionated booster dose of up to 3 × 10⁶ CAR T cells/kg at least 100 days after the first infusion. The primary endpoints were overall response rate 100 days after first infusion and the proportion of patients developing cytokine-release syndrome or neurotoxic events in the first 30 days after receiving treatment.
Key Findings
At a planned interim analysis of response rate (cutoff in October 2021), median follow-up was 12.1 months (interquartile range [IQR] = 9.1–13.5 months). The overall response rate during the first 100 days from infusion among the 30 patients was 100%, including 24 (80%) with very good partial response or better, 15 (50%) with complete response, 9 (30%) with very good partial response, and 6 (20%) with partial response.
At a median follow-up of 18 months (IQR = 15–20 months), the overall response rate was 100%, with complete response in 67% of patients, very good partial response in 27%, and partial response in 7%. Median duration of response was not reached (95% confidence interval [CI] = 12.9 months to not reached). Median progression-free survival was 14.5 months (95% CI = 12.8 months to not reached), with a 12-month rate of 70% (95% CI = 55%–89%). Median overall survival was not reached (95% CI = 8.0 months to not reached), with a 12-month rate of 86.5% (95% CI = 75.1%–99.7%).
Cytokine-release syndrome was observed in 24 patients (80%; all grade 1 or 2). No neurotoxic adverse events were observed. Persistent grade 3 or 4 cytopenias were observed in 20 patients (67%), and infections were reported in 20 patients (67%); of 45 infection events, 7 (16%) were grade ≥ 3. Death occurred in two patients in absence of disease progression, due to head injury and COVID-19 infection.
The investigators 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.”
Carlos Fernández de Larrea, MD, of Hospital Clínic de Barcelona, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by the Instituto de Salud Carlos III, Fundación La Caixa, and Fundació Bosch i Aymerich. For full disclosures of the study authors, visit thelancet.com.
