An academic chimeric antigen receptor (CAR) T-cell therapy, ARI0002h, produced durable responses in patients with relapsed or refractory multiple myeloma, according to data presented at the EHA 2022 Hybrid Congress.
These responses were seen in the absence of neurotoxicity, said study presenter Carlos Fernandez De Larrea, MD, PhD, of Hospital Clinic Barcelona in Spain.
Dr Fernandez De Larrea explained that ARI0002h was entirely developed at an academic institution. It is a lentiviral autologous CAR T-cell product with a 4-1BB costimulatory domain and a humanized single chain variable fragment targeting BCMA.
Researchers investigated ARI0002h in a multicenter, phase 1/2 trial (ClinicalTrials.gov Identifier: NCT04309981) of 30 patients with relapsed or refractory multiple myeloma. The patients had received 2 or more prior regimens, including a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 antibody.
The patients’ median age at baseline was 61 years (range, 36-74 years), and most were men (n=18). The median number of prior therapies was 4 (range, 2-10), and all patients had prior transplant.
Thirty patients received at least 1 dose of ARI0002h, and 50% of them required bridging therapy. A second dose of ARI0002h was planned at least 4 months after the first dose in patients who achieved a response and had no serious complications after the first dose.
The researchers used a targeted dose of 3×106 CAR-T cells/kg, administered in a fractionated manner. The median production time for ARI0002h was 11 days (range, 9-14 days).
After the first dose, the overall response rate was 100%, with 63% of patients achieving a stringent complete remission, 30% having a very good partial response, and 7% having a partial response.
At a median follow-up of 17.5 months, the median progression-free survival (PFS) and median overall survival (OS) were not reached. The 18-month PFS rate was 53%, and the 18-month OS rate was 73%.
Cytokine release syndrome (CRS) occurred in 90% of patients, but there were no grade 3-5 CRS events. The median onset of CRS was 8 days, and the median duration of CRS was 4 days. There was no neurotoxicity.
All patients had cytopenias beyond 30 days after infusion. All patients had grade 3/4 thrombocytopenia, 69% had grade 3/4 neutropenia, and 52% hade grade 3/4 anemia.
Twenty-four patients received a second infusion of ARI0002h, and 14 of these patients already had a stringent CR at the time. Six patients had an improved response after reinfusion. There were no cases of CRS or neurotoxicity after the second infusion.
“ARI0002h, an academic humanized CAR-T against BCMA, is a promising therapy for patients with relapsed or refractory multiple myeloma,” Dr Fernandez De Larrea said.
He noted that, while he did not have exact figures on the cost of ARI0002h, “as you can imagine, it is cheaper than commercial options.”
Disclosures: The presenter declared affiliations with Amgen, Bristol Myers Squibb, Janssen, Pfizer, Sanofi, GSK, and Takeda.
Fernandez De Larrea C, Gonzalez-Calle V, Oliver-Caldes A, et al. Efficacy and safety of ARI0002H, an academic BCMA-directed CAR-T cell therapy with fractionated initial therapy and booster dose in patients with relapsed/refractory multiple myeloma. Presented at EHA 2022; June 9-12, 2022. Abstract S103.