By Mary Ellen Schneider
Axicabtagene ciloleucel (axi-cel) appeared effective and well tolerated as first-line therapy for high-risk large B-cell lymphoma in the phase 2 ZUMA-12 study, which was presented at the annual meeting of the American Society of Hematology.
ZUMA-12 is the first study to evaluate chimeric antigen receptor (CAR) T-cell therapy as first-line therapy for high-risk large B-cell lymphomas (Abstract 405). In an interim analysis, axi-cel achieved high overall and complete response rates. Axi-cel is already approved in the United States and the European Union for the treatment of relapsed/refractory aggressive B-cell non-Hodgkin lymphoma after at least two lines of systemic therapy.
“Our results show that axi-cel may be safely administered and demonstrates substantial clinical benefit in patients with an unmet medical need,” said Sattva S. Neelapu, MD, of the University of Texas MD Anderson Cancer Center in Houston, who presented the study findings.
Patients in the study underwent leukapheresis and optional non-chemotherapy bridging at the discretion of the investigator, followed by conditioning chemotherapy with cyclophosphamide and fludarabine. Treatment with axi-cel was given as a single infusion, with a target dose of 2 x 106 CAR T cells/kg.
The researchers enrolled and leukapheresed a total of 37 patients. As of data cutoff on Aug. 25, 2020, 32 patients had received conditioning chemotherapy and axi-cel treatment. Three patients were awaiting axi-cel infusion and two patients were withdrawn from the study. A total of 32 patients were evaluable for safety at median follow up of 9.5 months and 27 patients were evaluable for efficacy at a median follow up of 9.3 months.
The median age of study participants was 61 years and most of the patients had advanced stage disease.
Overall, the objective response rate was 85% and the complete response rate was 74%. The median time to both initial objective response and complete response was 1 month. In total, four patients converted from partial response to complete response, and one patient converted from stable disease to complete response. Dr. Neelapu reported that 70% of patients had an ongoing response as of data cutoff.
Median duration of response, progression-free survival, and overall survival were not reached at a median follow-up of 9.5 months.
The most common axi-cel-related serious adverse events were encephalopathy (16%), elevated alanine aminotransferase (9%), and decreased neutrophil count (9%). One death occurred during the study due to COVID-19. All 32 patients developed cytokine release syndrome (CRS), but just 9% had grade 3 CRS. The median time to onset of CRS was 4 days and the median duration was 6 days. All cases of CRS resolved. Neurological adverse events of grade 3 or 4 occurred in 25% of patients.
In ZUMA-12, the researchers observed a higher frequency of CCR7+CD45RA+ T cells in the pre-infusion product, which was associated with greater expansion of CAR T cells as compared with the pivotal ZUMA-1 trial. This suggests improved T cell fitness in first-line treatment, Dr. Neelapu said.