Axicabtagene ciloleucel (Yescarta), an anti-CD19 chimeric antigen receptor T-cell therapy (CAR-T), had durable responses in patients with relapsed or refractory large B-cell lymphoma, according to 2-year follow-up data from the single-arm, multicenter, phase 1/2 ZUMA-1 trial (ClinicalTrials.gov Identifier: NCT02348216).1 The trial data were published in Lancet Oncology.
The ZUMA-1 trial enrolled adults with relapsed or refractory large B-cell lymphoma from 22 sites in the United States and Israel. Patients received a chemotherapy regimen of fludarabine and cyclophosphamide followed by a single infusion of axicabtagene ciloleucel.
A total of 119 patients were enrolled and 108 received axicabtagene ciloleucel; 101 patients were evaluable at follow-up. Data were previously reported for a median follow-up of 15.4 months. The current study reported data at a median follow-up of 27.1 months, or about 2 years.
At a 2-year follow-up, 84 patients (83%) had an investigator-assessed objective response, 59 (58%) of which had a complete response. Thirty-nine patients (39%) had an investigator-assessed ongoing response, with a median duration of response of 11.1 months (range, 4.2 to not estimable). The median overall survival was not yet reached (range, 12.8 to not estimable). Patients had a median progression-free survival of 5.9 months (95% CI, 3.3-15.0).
Additional serious adverse events emerged at 2-year follow-up for 4 patients, which included grade 3 mental status changes, grade 4 myelodysplastic syndrome, grade 3 lung infection, and 2 episodes of grade 3 bacteremia. The study authors asserted that none of the serious adverse events were treatment related.
Fifty patients died from progressive disease while on study, with 6 deaths occurring during the first 1-year follow-up analysis. Four patient deaths were related to adverse events, 2 of which were related to treatment with axicabtagene ciloleucel. The patient deaths had been previously reported in the 1-year follow-up analysis.
“These 2-year follow-up data from ZUMA-1 suggest that axicabtagene ciloleucel can induce durable responses and a median overall survival of greater than 2 years, and has a manageable long-term safety profile in patients with relapsed or refractory large B-cell lymphoma,” the study authors wrote in conclusion.
- Locke FL, Ghobadi A, Jacobson CA, et al. Long-term safety and activity of axicabtagene ciloleucel in refractory large B-cell lymphoma (ZUMA-1): A single-arm, multicentre, phase 1–2 trial. Lancet Oncol. 2019;20(1):31-42.