T Cells Expressing a Novel Fully-Human Anti-BCMA CAR for Treating Multiple Myeloma

Patients with relapsed multiple myeloma were treated with fully-human heavy-chain-only CAR T cells (FHVH-T) targeting B-cell Maturation Antigen (BCMA), a protein expressed by multiple myeloma cells. In this first-in-humans clinical trial, eligible patients were treated with a pre-conditional chemotherapy regimen of 30mg/m2 fludaribine and 300mg/m2 cyclophosphamide at days -5 and -3. FHVH-T was infused into the patients at day 0. A range of doses 0.75x10^6, 1.5x10^6, 3x10^6, 6x10^6, and 12x10^6 CAR+ T cells/kg of patient bodyweight were tested. After testing, a dose of 6x10^6 CAR+ T cells/kg was used. Patients were followed using immunological techniques such as flow cytometry and multicytokine analyses. Molecular techniques such as quantitative real-time PCR and single cell RNA sequencing were also performed. FHVH-T induced rapid clearance of multiple myeloma cells. The overall response rate was 92%, the stringent complete response rate was 52%, and the median progression-free survival was 78 weeks. Primarily, single cell RNA sequencing data from four patients treated with FHVH-T will be made available through dbGaP. This clinical trial is registered on clinicaltrials.gov as NCT03602612.