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T Cells Genetically Modified to Express an Anti–B-Cell Maturation Antigen Chimeric Antigen Receptor Cause Remissions of Poor-Prognosis Relapsed Multiple Myeloma
Open accessAbstract
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 × 10 6 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.
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Metadata
- Authors
- Brudno, J. N., Maric, I., Hartman, S. D., Rose, J. J., Wang, M., Lam, N., Stetler-Stevenson, M., Salem, D., Yuan, C., Pavletic, S., Kanakry, J. A., Ali, S. A., Mikkilineni, L., Feldman, S. A., Stroncek, D. F., Hansen, B. G., Lawrence, J., Patel, R., Hakim, F., Gress, R. E., & Kochenderfer, J. N.
- Venue
- Journal of Clinical Oncology
- Published
- 2018-08-01
- Volume
- 36
- Issue
- 22
- Pages
- 2267-2280
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- OpenAlex
- W2807637103
- Cited by
- 781
- References
- 13
- FWCI
- 30.92
- Type
- journal article
- Language
- en
- Open access
- green
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