James N. Kochenderfer1, Mark E. Dudley1, Sadik H. Kassim1, Robert Somerville1, Robert O. Carpenter1, Maryalice Stetler‐Stevenson1, James C. Yang1, Giao Q. Phan1, Marybeth S. Hughes1, Richard M. Sherry1, Mark Raffeld1, Steven A. Feldman1, Lily Lu1, Yong F. Li1, Lien T. Ngo1, André Goy1, Tatyana Feldman1, David Spaner1, Michael Wang1, Clara C. Chen1, Sarah M. Kranick1, Avindra Nath1, Debbie-Ann N. Nathan1, Kathleen E. Morton1, Mary Ann Toomey1, Steven A. Rosenberg1
1James N. Kochenderfer, Mark E. Dudley, Sadik H. Kassim, Robert P.T. Somerville, Robert O. Carpenter, Maryalice Stetler-Stevenson, James C. Yang, Q. Phan, Marybeth S. Hughes, Richard M. Sherry, Mark Raffeld, Steven Feldman, Lily Lu, Yong F. Li, Lien T. Ngo, Debbie-Ann N. Nathan, Kathleen E. Morton, Mary Ann Toomey, and Steven A. Rosenberg, National Cancer Institute; Clara C. Chen, Clinical Center, National Institutes of Health (NIH); Sarah M. Kranick and Avindra Nath, National Institutes of Neurologic...
Tóm tắt
Purpose T cells can be genetically modified to express an anti-CD19 chimeric antigen receptor (CAR). We assessed the safety and efficacy of administering autologous anti-CD19 CAR T cells to patients with advanced CD19+ B-cell malignancies. Patients and Methods We treated 15 patients with advanced B-cell malignancies. Nine patients had diffuse large B-cell lymphoma (DLBCL), two had indolent lymphomas, and four had chronic lymphocytic leukemia. Patients received a conditioning chemotherapy regimen of cyclophosphamide and fludarabine followed by a single infusion of anti-CD19 CAR T cells. Results Of 15 patients, eight achieved complete remissions (CRs), four achieved partial remissions, one had stable lymphoma, and two were not evaluable for response. CRs were obtained by four of seven evaluable patients with chemotherapy-refractory DLBCL; three of these four CRs are ongoing, with durations ranging from 9 to 22 months. Acute toxicities including fever, hypotension, delirium, and other neurologic toxicities occurred in some patients after infusion of anti-CD19 CAR T cells; these toxicities resolved within 3 weeks after cell infusion. One patient died suddenly as a result of an unknown cause 16 days after cell infusion. CAR T cells were detected in the blood of patients at peak levels, ranging from nine to 777 CAR-positive T cells/μL. Conclusion This is the first report to our knowledge of successful treatment of DLBCL with anti-CD19 CAR T cells. These results demonstrate the feasibility and effectiveness of treating chemotherapy-refractory B-cell malignancies with anti-CD19 CAR T cells. The numerous remissions obtained provide strong support for further development of this approach.
