Long-Duration Complete Remissions of Diffuse Large B Cell Lymphoma after Anti-CD19 Chimeric Antigen Receptor T Cell Therapy
| Autor: | Norris Lam, Steven A. Rosenberg, John J. Rossi, James N. Kochenderfer, Adrian Bot, Robert Somerville, James Chih-Hsin Yang, Richard M. Sherry, Steven A. Feldman, Lori McIntyre, Tangying Lu |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Adult Male Cyclophosphamide T-Lymphocytes Antigens CD19 Receptors Antigen T-Cell Immunotherapy Adoptive 03 medical and health sciences 0302 clinical medicine immune system diseases hemic and lymphatic diseases Drug Discovery Genetics medicine Humans Molecular Biology B cell Pharmacology B-Lymphocytes business.industry Middle Aged medicine.disease Chimeric antigen receptor Lymphoma Fludarabine Immunoglobulin A 030104 developmental biology medicine.anatomical_structure Polyclonal B cell response Immunoglobulin M 030220 oncology & carcinogenesis Immunoglobulin G Immunology Commentary Molecular Medicine Chimeric Antigen Receptor T-Cell Therapy Female Lymphoma Large B-Cell Diffuse business Diffuse large B-cell lymphoma Vidarabine medicine.drug |
| Zdroj: | Molecular therapy : the journal of the American Society of Gene Therapy. 25(10) |
| ISSN: | 1525-0024 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|