CD19 CAR T cells following autologous transplantation in poor-risk relapsed and refractory B-cell non-Hodgkin lymphoma

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.