T cells expressing an anti-B-cell maturation antigen chimeric antigen receptor cause remissions of multiple myeloma

Therapies with novel mechanisms of action are needed for multiple myeloma (MM). B-cell maturation antigen (BCMA) is expressed in most cases of MM. We conducted the first-inhumans clinical trial of chimeric antigen receptor (CAR) T cells targeting BCMA. T cells expressing the CAR used in this work (CAR-BCMA) specifically recognized BCMAexpressing cells. Twelve patients receivedCAR-BCMAT cells in this dose-escalation trial. Amongthe 6 patients treated on the lowest 2 dose levels, limited antimyelomaactivity and mild toxicity occurred.Onthe third dose level, 1 patient obtained a very good partial remission.Twopatients were treatedon the fourth dose level of 9 3 106 CAR1 T cells/kg body weight. Before treatment, the first patient on the fourth dose level had chemotherapyresistant MM, making up 90% of bone marrow cells. After treatment, bone marrow plasma cells became undetectable by flow cytometry, and the patient'sMMentered a stringent complete remission that lasted for 17 weeks before relapse. The second patient on the fourth dose level had chemotherapy-resistantMMmaking up80%of bone marrow cells before treatment. Twenty-eight weeks after this patient received CAR-BCMA T cells, bone marrow plasma cells were undetectable by flow cytometry, and the serum monoclonal protein had decreased by >95%. This patient is in an ongoing very good partial remission. Both patients treated on the fourth dose level had toxicity consistent with cytokine-releasesyndrome including fever, hypotension, and dyspnea. Both patients hadprolonged cytopenias. Our findings demonstrate antimyeloma activity of CAR-BCMA T cells.