Early-Stage Clinical Study of Novel BCMA CAR T-Cell Therapy in Resistant Myeloma
Posted: Friday, August 23, 2019
The results of an early-stage clinical study presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract 8013) suggest that a novel B-cell maturation antigen (BCMA) targeting chimeric antigen receptor (CAR) T-cell therapy may prove to be safe and active in relapsed or refractory multiple myeloma. The new therapy, CT103A, reportedly achieves “transient, manageable, and reversible” adverse events by utilizing a lentiviral vector containing a CAR structure with a fully human single-chain variable fragment, CD8a hinger and transmembrane, 4-1BB co-stimulatory, and CD3z activation domains.
“A 100% [overall response rate] and a rapid response within 2 weeks suggest CT103A could be developed as a competitive therapeutic to treat patients with [relapsed or refractory multiple myeloma],” concluded Jianfeng Zhou, MD, of the Tongji Medical College at the Huazhong University of Science and Technology, Wuhan, China, and colleagues.
In this single-center, single-arm trial, patients diagnosed with relapsed or refractory multiple myeloma were treated with a 3 + 3 dose-escalation trial of CT103A. Patients were administered three doses at 1, 3, and 6 x 10 kg of CT103A after receiving a conditioning chemotherapy regimen of cyclophosphamide and fludarabine. All nine of the patients in the trial had previously received four prior lines of therapy.
At the time of the February 2019 data analysis, the overall response rate was 100%, with all patients exhibiting a response within 14 days and 67% of the patients achieving a complete or stringent complete response at the lowest dose of CT103A. The investigators observed a robust expansion, even at the lowest dosage level, the authors observed.
For patients in the first two dose groups, grade 0 to 2 cytokine-release syndrome was observed. For patients treated with 6 doses of 10 kg, one patient experienced dose-limiting toxicity.
Disclosure: The study authors’ disclosure information may be found at coi.asco.org.