Long-Duration Complete Remissions of Diffuse Large B Cell Lymphoma after Anti-CD19 Chimeric Antigen Receptor T Cell Therapy

James N. Kochenderfer, Robert P.T. Somerville, Tangying Lu, James C. Yang, Richard M. Sherry, Steven A. Feldman, Lori McIntyre, Adrian Bot, John Rossi, Norris Lam, Steven A. Rosenberg

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
JournalMolecular Therapy
DOIs
StateAccepted/In press - 2017
Externally publishedYes

Keywords

  • Adoptive T cell therapy
  • Chimeric antigen receptors
  • Lymphoma

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

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    Kochenderfer, J. N., Somerville, R. P. T., Lu, T., Yang, J. C., Sherry, R. M., Feldman, S. A., McIntyre, L., Bot, A., Rossi, J., Lam, N., & Rosenberg, S. A. (Accepted/In press). Long-Duration Complete Remissions of Diffuse Large B Cell Lymphoma after Anti-CD19 Chimeric Antigen Receptor T Cell Therapy. Molecular Therapy. https://doi.org/10.1016/j.ymthe.2017.07.004