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

High-dose chemotherapy and autologous stem cell transplantation (HDT-ASCT) is the standard of care for relapsed or primary refractory (rel/ref) chemorefractory diffuse large B-cell lymphoma. Only 50% of patients are cured with this approach. We investigated safety and efficacy of CD19-specific chimeric antigen receptor (CAR) T cells administered following HDT-ASCT. Eligibility for this study includes poor-risk rel/ref aggressive B-cell non-Hodgkin lymphoma chemosensitive to salvage therapy with: (1) positron emission tomography–positive disease or (2) bone marrow involvement. Patients underwent standard HDT-ASCT followed by 19-28z CAR T cells on days +2 and +3. Of 15 subjects treated on study, dose-limiting toxicity was observed at both dose levels (5 x 106 and 1 x 107 19-28z CAR T per kilogram). 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 = .05) but not peak CAR T-cell expansion. Serum interferon- elevation (P < .001) and possibly interleukin-10 (P = .07) were associated with toxicity. The 2-year progression-free survival (PFS) is 30% (95% confidence interval, 20% to 70%).  Subjects given decreased naive-like (CD45RA+CCR7+) CD4+ and CD8+ CAR T cells experienced superior PFS (P = .02 and .04, respectively). There was no association between...

Source: Blood - August 14, 2019 Category: Hematology Authors: Sauter, C. S., Senechal, B., Riviere, I., Ni, A., Bernal, Y., Wang, X., Purdon, T., Hall, M., Singh, A. N., Szenes, V. Z., Yoo, S., Dogan, A., Wang, Y., Moskowitz, C. H., Giralt, S., Matasar, M. J., Perales, M.-A., Curran, K. J., Park, J., Sadelain, M., B Tags: Immunobiology and Immunotherapy, Transplantation, Lymphoid Neoplasia, Clinical Trials and Observations Source Type: research