• James N Kochenderfer, Somerville Robert P T RPT Surgery Branch, National Cancer Institute, Bethesda, MD 20892, USA., Tangying Lu, James C Yang, Richard M Sherry, Steven A Feldman, Lori McIntyre, Adrian Bot, John Rossi, Norris Lam, and Steven A Rosenberg.
• Experimental Transplantation and Immunology Branch, National Cancer Institute, Bethesda, MD 20892, USA. Electronic address: kochendj@mail.nih.gov.
• Mol. Ther. 2017 Oct 4; 25 (10): 2245-2253.

AbstractT 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.Published by Elsevier Inc.

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