Posted: Tuesday, February 8, 2022
According to research presented in the Journal of Hematology & Oncology, bispecific BM38 chimeric antigen receptor (CAR) T-cell therapy may be a safe and effective treatment option for patients with refractory or relapsed multiple myeloma. It may particularly benefit those with comorbidities, such as unfavorable cytogenetic abnormalities or extramedullary disease, who typically experience worse survival outcomes, according to the researchers.
“BM38 CAR-Ts showed significant in vivo persistence, deep and durable responses, and effective elimination of [extramedullary disease],” concluded Yu Hu, MD, PhD, of Union Hospital, Huazhong University of Science and Technology in Wuhan, and colleagues.
The phase I trial included in vitro and in vivo testing of the antimyleoma activity of BM38 CAR T cells using a constructed, humanized BC38 CAR-targeting B-cell maturation antigen (BCMA) and CD38. Infusions of BM38 CAR T cells were administered to 23 patients with refractory or relapsed multiple myeloma. Bispecific CAR T cells were found to be more cytotoxic in in vitro mouse models than were monospecific BCMA or CD38 CAR T cells.
At a median follow-up of 9 months, 87% of patients (n = 20) achieved a clinical response and measurable residual disease negativity. A total of 12 patients achieved a complete response. More than half of patients (56%) experienced complete eradication of extramedullary plasmacytoma, whereas 33% experienced partial elimination. Bispecific CAR T cells remained detectable in 77.8% of evaluable patients. At a follow-up of 12 months, BM38 CAR T cells remained detectable in 62.2% of patients. The median progression-free survival was 17.2 months.
Hematologic toxicities were frequently noted, including neutropenia (96%), leukopenia (87%), anemia (43%), and thrombocytopenia (61%). A total of 20 patients (87%) experienced cytokine-release syndrome; 65% of these cases were grade 1 or 2. The expression of BCMA and CD38 CAR T cells on multiple myeloma cells was observed in two patients who relapsed.
Disclosure: For full disclosures of the study authors, visit jhoonline.biomedcentral.com.