CD19 CAR T cells following autologous transplantation in poor-risk relapsed and refractory B-cell non-Hodgkin lymphoma
| Autor: | Craig S. Sauter, Sergio Giralt, Ahmet Dogan, Renier J. Brentjens, Xiuyan Wang, Kevin J. Curran, Yvette Bernal, Ashvin N. Singh, Craig H. Moskowitz, Jae H. Park, Brigitte Senechal, Malloury Hall, Terence J. Purdon, Victoria Szenes, Michel Sadelain, Ai Ni, Isabelle Riviere, Sarah Yoo, Matthew J. Matasar, Miguel-Angel Perales, Yongzeng Wang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Adult
Male medicine.medical_specialty Immunobiology and Immunotherapy medicine.medical_treatment Immunology Receptors Antigen T-Cell Biochemistry Gastroenterology Immunotherapy Adoptive Transplantation Autologous Autologous stem-cell transplantation Internal medicine medicine Autologous transplantation Humans Aged business.industry Cell Biology Hematology Immunotherapy Middle Aged medicine.disease Lymphoma Transplantation medicine.anatomical_structure Treatment Outcome Female Bone marrow Lymphoma Large B-Cell Diffuse Neoplasm Recurrence Local business Diffuse large B-cell lymphoma CD8 Stem Cell Transplantation |
| Zdroj: | Blood |
| Popis: | High-dose chemotherapy followed by autologous stem cell transplantation (HDT-ASCT) is the standard of care for relapsed or chemorefractory diffuse large B-cell lymphoma (rel/ref DLBCL). Only 50% of patients are cured with this approach. We investigated whether CD19-specific chimeric antigen receptor (CAR) T cells administered following HDT-ASCT may enhance progression-free survival (PFS). Methods: Eligibility for this study includes poor-risk rel/ref aggressive B-NHL chemosensitive to salvage therapy with: 1) FDG-PET (+) or 2) bone marrow involvement. Patients underwent BEAM conditioned HDT-ASCT and followed by 19-28z CAR-T cells on days +2 and +3. Results: Of 15 subjects treated on study, dose-limiting toxicity was observed at both dose levels (5 x106 and 1 x107 19-28z CAR-T/kg). Ten of 15 subjects experienced CAR T cell-induced neurotoxicity and/or cytokine-release syndrome (CRS), which were associated with greater CAR T cell persistence (p=0.05) but not peak CAR T cell expansion. Serum IFN-g elevation (pl0.001) and possibly IL-10 (p=0.07) were associated with toxicity. The 2-year PFS is 30% (95% CI: 20-70%). Two subjects with progression of disease (POD) were CD19 (-) on re-biopsy. Subjects given decreased naive-like (CD45RA+CCR7+) CD4+ and CD8+ CAR T cells experienced superior PFS (p=0.02 and 0.04, respectively). There was no association between CAR T cell peak expansion, persistence or cytokine changes and PFS. Conclusions: 19-28z CAR T cells following HDT-ASCT was associated with a high-incidence of reversible neurotoxicity and CRS. Following HDT-ASCT, effector CD4+ and CD8+ immunophenotypes may improve disease control. Phenotype selection and/or multiple infusions may be the focus of the next clinical trial. This study is registered at www.clinicaltrials.gov as #NCT01840566. |
| Databáze: | OpenAIRE |
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