CAR T Cells Targeting B-Cell Maturation Antigen in Poor-Prognosis Relapsed Multiple Myeloma
In a first-in-human study reported in the Journal of Clinical Oncology, Brudno et al found that chimeric antigen receptor (CAR) autologous T cells targeting B-cell maturation antigen (BCMA) produced responses in patients with poor-prognosis relapsed multiple myeloma.
Study Details
The current report involves 16 patients who received the highest study dose level of 9 x 106 CAR-BCMA T cells/kg. Patients had received a median of 9.5 prior lines of therapy for multiple myeloma, and 63% had disease refractory to the last treatment regimen received. Infusion of CAR-BCMA T cells was given after a conditioning regimen of cyclophosphamide and fludarabine.
Among the 16 patients, 13 (81%) had partial responses or better, with 10 (63%) having a very good partial response or complete response. All except 1 patient had substantial decreases in serum multiple myeloma marker levels. At the time of analysis, responses were ongoing in 6 patients. Median event-free survival was 31 weeks.
Higher peak blood CAR T-cell levels were associated with response. Responses included eradication of extensive bone marrow disease and resolution of soft-tissue plasmacytomas. All 11 patients with a partial response or better who were evaluable for minimal residual disease achieved bone marrow minimal residual disease–negative status. At 6 to 9 days postinfusion, CAR-BCMA T cells in the blood were predominantly highly differentiated CD8-positive T cells.
Cytokine-Release Syndrome
Cytokine-release syndrome toxicities were severe in some patients, but were reversible. More severe cytokine-release syndrome toxicities were observed in patients with a higher percentage of bone marrow multiple myeloma plasma cells.
Vasopressor support for hypotension was required in 6 patients (39%), and mechanical ventilation was needed in 1. Tocilizumab (Actemra) was required in 5 patients (31%), and corticosteroids were required in 4 (25%).
The investigators concluded, “CAR-BCMA T cells had substantial activity against heavily treated relapsed/refractory [multiple myeloma]. Our results should encourage additional development of CAR T-cell therapies for [multiple myeloma].”
James N. Kochenderfer, MD, of the National Institutes of Health, is the corresponding author for the Journal of Clinical Oncology article.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
