TY - JOUR
T1 - Long-Duration Complete Remissions of Diffuse Large B Cell Lymphoma after Anti-CD19 Chimeric Antigen Receptor T Cell Therapy
AU - Kochenderfer, James N.
AU - Somerville, Robert P.T.
AU - Lu, Tangying
AU - Yang, James C.
AU - Sherry, Richard M.
AU - Feldman, Steven A.
AU - McIntyre, Lori
AU - Bot, Adrian
AU - Rossi, John
AU - Lam, Norris
AU - Rosenberg, Steven A.
N1 - Publisher Copyright:
© 2017
PY - 2017/10/4
Y1 - 2017/10/4
N2 - T cells expressing anti-CD19 chimeric antigen receptors (CARs) can induce complete remissions (CRs) of diffuse large B cell lymphoma (DLBCL). The long-term durability of these remissions is unknown. We administered anti-CD19 CAR T cells preceded by cyclophosphamide and fludarabine conditioning chemotherapy to patients with relapsed DLBCL. Five of the seven evaluable patients obtained CRs. Four of the five CRs had long-term durability with durations of remission of 56, 51, 44, and 38 months; to date, none of these four cases of lymphomas have relapsed. Importantly, CRs continued after recovery of non-malignant polyclonal B cells in three of four patients with long-term complete remissions. In these three patients, recovery of CD19+ polyclonal B cells took place 28, 38, and 28 months prior to the last follow-up, and each of these three patients remained in CR at the last follow-up. Non-malignant CD19+ B cell recovery with continuing CRs demonstrated that remissions of DLBCL can continue after the disappearance of functionally effective anti-CD19 CAR T cell populations. Patients had a low incidence of severe infections despite long periods of B cell depletion and hypogammaglobulinemia. Only one hospitalization for an infection occurred among the four patients with long-term CRs. Anti-CD19 CAR T cells caused long-term remissions of chemotherapy-refractory DLBCL without substantial chronic toxicities. Five of seven patients receiving anti-CD19 chimeric antigen receptor (CAR) T cells obtained complete remissions. Four of the five CRs had long-term durability with durations of remissions ranging from 38 to 56 months. Remissions persisted despite recovery of normal B cells in three of the four patients with long-term remissions.
AB - T cells expressing anti-CD19 chimeric antigen receptors (CARs) can induce complete remissions (CRs) of diffuse large B cell lymphoma (DLBCL). The long-term durability of these remissions is unknown. We administered anti-CD19 CAR T cells preceded by cyclophosphamide and fludarabine conditioning chemotherapy to patients with relapsed DLBCL. Five of the seven evaluable patients obtained CRs. Four of the five CRs had long-term durability with durations of remission of 56, 51, 44, and 38 months; to date, none of these four cases of lymphomas have relapsed. Importantly, CRs continued after recovery of non-malignant polyclonal B cells in three of four patients with long-term complete remissions. In these three patients, recovery of CD19+ polyclonal B cells took place 28, 38, and 28 months prior to the last follow-up, and each of these three patients remained in CR at the last follow-up. Non-malignant CD19+ B cell recovery with continuing CRs demonstrated that remissions of DLBCL can continue after the disappearance of functionally effective anti-CD19 CAR T cell populations. Patients had a low incidence of severe infections despite long periods of B cell depletion and hypogammaglobulinemia. Only one hospitalization for an infection occurred among the four patients with long-term CRs. Anti-CD19 CAR T cells caused long-term remissions of chemotherapy-refractory DLBCL without substantial chronic toxicities. Five of seven patients receiving anti-CD19 chimeric antigen receptor (CAR) T cells obtained complete remissions. Four of the five CRs had long-term durability with durations of remissions ranging from 38 to 56 months. Remissions persisted despite recovery of normal B cells in three of the four patients with long-term remissions.
KW - adoptive T cell therapy
KW - chimeric antigen receptors
KW - lymphoma
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U2 - 10.1016/j.ymthe.2017.07.004
DO - 10.1016/j.ymthe.2017.07.004
M3 - Article
C2 - 28803861
AN - SCOPUS:85028330613
SN - 1525-0016
VL - 25
SP - 2245
EP - 2253
JO - Molecular Therapy
JF - Molecular Therapy
IS - 10
ER -