Anti-CD19 chimeric antigen receptor (CAR) T-cells were determined to be safe for further study in patients with refractory aggressive non-Hodgkin lymphoma, according to updated data from a phase 1/2 study presented at the American Academy for Cancer Research (AACR) Annual Meeting 2016.1
A previous study by Kochenderfer et al published in the Journal of Clinical Oncology in 2014 demonstrated durable remissions with anti-CD19 CAR T-cells in patients with relapsed/refractory advanced B-cell malignancies. In this study, researchers sought to evaluate the same CAR construct in patients with non-Hodgkin lymphoma.
For the multicenter, phase 1/2 ZUMA trial, researchers enrolled 7 patients with refractory aggressive diffuse large B-cell lymphoma, most of whom experienced disease relapse within 12 months of autologous hematopoietic cell transplantation. After participants were given a fixed-dose conditioning chemotherapy regimen consisting of cyclophosphamide and fludarabine, they then received anti-CD19 CAR T-cells at a target dose of 2 x 106 cells/kg.
Results showed that after a median follow-up of 13 weeks after CAR T-cell infusion, 1 patient experienced grade 4 encephalopathy and grade 3 cytokine release syndrome. This patient died due to intracranial hemorrhage that was deemed unrelated to immunotherapy. Four patients experienced grade 3 treatment-related adverse events, but all resolved. Two patients experienced no treatment-related adverse events.
The predominant toxicities appeared to be cytokine release syndrome and neurotoxicity, which were generally reversible with interleukin-6 receptor subunit alpha precursor (α-IL6R) and steroids.
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With respect to efficacy, 4 patients achieved complete remission, 3 of which were ongoing for more than 3 months, 1 patient had a partial response, and 1 patient had stable disease.
The potentially pivotal phase 2 portion of the ZUMA study is ongoing.
- Ghodabi A, Locke FL, Neelapu SS, et al. Updated phase I results from ZUMA-1: a phase I-II multicenter study evaluating the safety and efficacy of KTE-C19 (anti-CD19 CAR T cells) in subjects with refractory aggressive non-Hodgkin lymphoma (NHL). Oral presentation at: AACR Annual Meeting 2016; April 16-20, 2016; New Orleans, LA.