Safety and feasibility of CD19 CAR TCM therapy post-myeloablative hematopoietic stem cell transplantation (HSCT) were established in patients with relapsed intermediate-grade B-cell non Hodgkin lymphoma, according to results of 2 phase 1 studies published in Blood.1
HSCT is a mainstay of therapy for patients with relapsed intermediate-grade B-cell non Hodgkin lymphoma, however relapse rates are high. Investigators conducted 2 phase 1 studies to improve long-term remission rates. Patients were administered adoptive T-cell immunotherapy post HSCT, using ex vivo-expanded autologous central-memory-enriched T cells (Tcm) transduced with lentivirus expressing CD19-specific chimeric antigen receptors (CARs).
Results from NHL1 and NHL2 were safety/feasibility studies investigating different T cell populations and CAR constructs. Engineered TCM-derived CD19-CAR T cells were infused 2 days post-HSCT at doses of 25 to 200 x106 in a single infusion.
In the NHL1 study, 8 patients safely received T cell products engineered from enriched CD8+TCM subsets, expressing a first-generation CD19 CAR containing only the CD3ζ endodomain (CD19:ζ). Four of 8 patients (95% CI, 16 – 84) were progression free at 1 and 2 years.
In the NHL2 study, 8 patients safety received T cell products engineered from enriched CD4+ and CD8+TCM subsets and expressing a second-generation CD19 CAR containing the CD28 and CD3ζ endodomains (CD19:28ζ). Results showed that 6 of 8 patients (75%) were progression-free at 1 year (95% CI, 35 – 97). The CD4+/CD8+ TCM-derived CD19 CAR T cells (NHL2) exhibited improvement in CAR T cell expansion, but only lasted for a maximum of 28 days.
Neither cytokine release syndrome nor delayed hematopoietic engraftment was observed in either study.
- Wang X, Popplewell LL, Wagner JR, et al. Phase I studies of central-memory-derived CD19 CAR T cell therapy following autologous HSCT in patients with B-cell NHL [published online ahead of print April 26, 2016]. Blood. doi: 10.1182/blood-2015-12-686725.