| Literature DB >> 29812997 |
Jennifer N Brudno1, Irina Maric1, Steven D Hartman1, Jeremy J Rose1, Michael Wang1, Norris Lam1, Maryalice Stetler-Stevenson1, Dalia Salem1, Constance Yuan1, Steven Pavletic1, Jennifer A Kanakry1, Syed Abbas Ali1, Lekha Mikkilineni1, Steven A Feldman1, David F Stroncek1, Brenna G Hansen1, Judith Lawrence1, Rashmika Patel1, Frances Hakim1, Ronald E Gress1, James N Kochenderfer1.
Abstract
Purpose Therapies with novel mechanisms of action are needed for multiple myeloma (MM). T cells can be genetically modified to express chimeric antigen receptors (CARs), which are artificial proteins that target T cells to antigens. B-cell maturation antigen (BCMA) is expressed by normal and malignant plasma cells but not normal essential cells. We conducted the first-in-humans clinical trial, to our knowledge, of T cells expressing a CAR targeting BCMA (CAR-BCMA). Patients and Methods Sixteen patients received 9 × 106 CAR-BCMA T cells/kg at the highest dose level of the trial; we are reporting results of these 16 patients. The patients had a median of 9.5 prior lines of MM therapy. Sixty-three percent of patients had MM refractory to the last treatment regimen before protocol enrollment. T cells were transduced with a γ-retroviral vector encoding CAR-BCMA. Patients received CAR-BCMA T cells after a conditioning chemotherapy regimen of cyclophosphamide and fludarabine. Results The overall response rate was 81%, with 63% very good partial response or complete response. Median event-free survival was 31 weeks. Responses included eradication of extensive bone marrow myeloma and resolution of soft-tissue plasmacytomas. All 11 patients who obtained an anti-MM response of partial response or better and had MM evaluable for minimal residual disease obtained bone marrow minimal residual disease-negative status. High peak blood CAR+ cell levels were associated with anti-MM responses. Cytokine-release syndrome toxicities were severe in some cases but were reversible. Blood CAR-BCMA T cells were predominantly highly differentiated CD8+ T cells 6 to 9 days after infusion. BCMA antigen loss from MM was observed. Conclusion CAR-BCMA T cells had substantial activity against heavily treated relapsed/refractory MM. Our results should encourage additional development of CAR T-cell therapies for MM.Entities:
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Year: 2018 PMID： 29812997 PMCID： PMC6067798 DOI： 10.1200/JCO.2018.77.8084
Source DB: PubMed Journal: J Clin Oncol ISSN： 0732-183X Impact factor: 44.544