Promising results [10.1016/j.ymthe.2016.10.020] from the phase 1 portion of a multi-center phase 1/2 clinical trial (ZUMA-1 study [https://clinicaltrials.gov/ct2/show/NCT02348216]) were published in the January issue of Molecular Therapy.
The experimental therapy, which uses chimeric antigen receptor (CAR) modified T cells to treat patients with refractory diffuse large B-cell lymphoma (DLBCL), led to a remarkable response rate in the study participants.
The goal of the phase 1 portion of the ZUMA-1 study was to determine the safety of axicabtagene ciloleucel (KTE-C19) as assessed by the frequency of dose-limiting toxicities in patients with diffuse large B-cell lymphoma who were refractory to prior therapy that included anti-CD20 therapy and an anthracycline-containing regimen. The study included patients who had highly refractory disease, with two to four prior treatments.
Axicabtagene ciloleucel (KTE-C19) caused expected, but manageable, toxicity over a median follow-up period of nine months. Of the 7 patients treated with axicabtagene ciloleucel (KTE-C19), 1 patient experienced dose-limiting toxicity of cytokine release syndrome and neurotoxicity.
Axicabtagene ciloleucel (KTE-C19) resulted in promising clinical activity. The overall response rate was 71 percent (5 of 7 patients). The treatment was also durable with 43 percent, or 3 patients remaining in complete remission after one year.
The promising phase 1 results led to the initiation of the phase 2 portion of the ZUMA-1 study in aggressive non-Hodgkin lymphoma, including diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma and transformed follicular lymphoma.
