The DOI matches its Crossref record; 13 of the 13 references it cites were found in a registry or an index.
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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Cites
Two subsets of memory T lymphocytes with distinct homing potentials and effector functions
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“T cells can be divided into four groups on the basis of T-cell memory phenotype.(40) CAR-BCMAT cells contained a larger fraction of cells with the more differentiated effector memory and effector memory RA phenotypes after infusion compared with before infusion.”
BackgroundChimeric Antigen Receptor T Cells for Sustained Remissions in Leukemia
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CD19 CAR–T cells of defined CD4+:CD8+ composition in adult B cell ALL patients
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Chimeric Antigen Receptor T Cells against CD19 for Multiple Myeloma
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Cited by
CAR-T cell therapy: current limitations and potential strategies
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Anti-BCMA CAR T-cell therapy bb2121 in relapsed or refractory multiple myeloma.
Raje, N., Berdeja, J., Lin, Y., Siegel, D., Jagannath, S., Madduri, D., Liedtke, M., Rosenblatt, J., Maus, M. V., Turka, A., et al. (2019) · New England Journal of Medicine · doi:10.1056/nejmoa1817226 · Cited by 1,730
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B cell maturation antigen–specific CAR T cells are clinically active in multiple myeloma
Cohen, A. D., Garfall, A. L., Stadtmauer, E. A., Melenhorst, J. J., Lacey, S. F., Lancaster, E., Vogl, D. T., Weiss, B. M., Dengel, K., Nelson, A., et al. (2019) · Journal of Clinical Investigation · doi:10.1172/jci126397 · Cited by 778
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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- 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., . . . Kochenderfer, J. N. (2018). T Cells Genetically Modified to Express an Anti–B-Cell Maturation Antigen Chimeric Antigen Receptor Cause Remissions of Poor-Prognosis Relapsed Multiple Myeloma. Journal of Clinical Oncology. https://doi.org/10.1200/jco.2018.77.8084
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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