| Literature DB >> 28291388 |
James N Kochenderfer1, Robert P T Somerville1, Tangying Lu1, Victoria Shi1, Adrian Bot1, John Rossi1, Allen Xue1, Stephanie L Goff1, James C Yang1, Richard M Sherry1, Christopher A Klebanoff1, Udai S Kammula1, Marika Sherman1, Arianne Perez1, Constance M Yuan1, Tatyana Feldman1, Jonathan W Friedberg1, Mark J Roschewski1, Steven A Feldman1, Lori McIntyre1, Mary Ann Toomey1, Steven A Rosenberg1.
Abstract
Purpose T cells genetically modified to express chimeric antigen receptors (CARs) targeting CD19 (CAR-19) have potent activity against acute lymphoblastic leukemia, but fewer results supporting treatment of lymphoma with CAR-19 T cells have been published. Patients with lymphoma that is chemotherapy refractory or relapsed after autologous stem-cell transplantation have a grim prognosis, and new treatments for these patients are clearly needed. Chemotherapy administered before adoptive T-cell transfer has been shown to enhance the antimalignancy activity of adoptively transferred T cells. Patients and Methods We treated 22 patients with advanced-stage lymphoma in a clinical trial of CAR-19 T cells preceded by low-dose chemotherapy. Nineteen patients had diffuse large B-cell lymphoma, two patients had follicular lymphoma, and one patient had mantle cell lymphoma. Patients received a single dose of CAR-19 T cells 2 days after a low-dose chemotherapy conditioning regimen of cyclophosphamide plus fludarabine. Results The overall remission rate was 73% with 55% complete remissions and 18% partial remissions. Eleven of 12 complete remissions are ongoing. Fifty-five percent of patients had grade 3 or 4 neurologic toxicities that completely resolved. The low-dose chemotherapy conditioning regimen depleted blood lymphocytes and increased serum interleukin-15 (IL-15). Patients who achieved a remission had a median peak blood CAR+ cell level of 98/μL and those who did not achieve a remission had a median peak blood CAR+ cell level of 15/μL ( P = .027). High serum IL-15 levels were associated with high peak blood CAR+ cell levels ( P = .001) and remissions of lymphoma ( P < .001). Conclusion CAR-19 T cells preceded by low-dose chemotherapy induced remission of advanced-stage lymphoma, and high serum IL-15 levels were associated with the effectiveness of this treatment regimen. CAR-19 T cells will likely become an important treatment for patients with relapsed lymphoma.Entities:
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Year: 2017 PMID： 28291388 PMCID： PMC5455597 DOI： 10.1200/JCO.2016.71.3024
Source DB: PubMed Journal: J Clin Oncol ISSN： 0732-183X Impact factor: 44.544