TY - JOUR
T1 - Lymphoma remissions caused by anti-CD19 chimeric antigen receptor T cells are associated with high serum interleukin-15 levels
AU - Kochenderfer, James N.
AU - Somerville, Robert P.T.
AU - Lu, Tangying
AU - Shi, Victoria
AU - Bot, Adrian
AU - Rossi, John
AU - Xue, Allen
AU - Goff, Stephanie L.
AU - Yang, James C.
AU - Sherry, Richard M.
AU - Klebanoff, Christopher A.
AU - Kammula, Udai S.
AU - Sherman, Marika
AU - Perez, Arianne
AU - Yuan, Constance M.
AU - Feldman, Tatyana
AU - Friedberg, Jonathan W.
AU - Roschewski, Mark J.
AU - Feldman, Steven A.
AU - McIntyre, Lori
AU - Toomey, Mary Ann
AU - Rosenberg, Steven A.
N1 - Publisher Copyright:
© 2017 by American Society of Clinical Oncology.
PY - 2017/6/1
Y1 - 2017/6/1
N2 - 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/mL and those who did not achieve a remission had a median peak blood CAR+ cell level of 15/mL (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.
AB - 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/mL and those who did not achieve a remission had a median peak blood CAR+ cell level of 15/mL (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.
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U2 - 10.1200/JCO.2016.71.3024
DO - 10.1200/JCO.2016.71.3024
M3 - Article
C2 - 28291388
AN - SCOPUS:85017643829
SN - 0732-183X
VL - 35
SP - 1803
EP - 1813
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 16
ER -