medwireNews: Autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy significantly improves overall survival (OS) versus standard care for patients with relapsed or refractory large B-cell lymphoma, show phase 3 trial findings reported simultaneously at the 2023 ASCO Annual Meeting in Chicago, Illinois, USA, and in The New England Journal of Medicine.
“ZUMA-7 confirms axi-cel [axicabtagene ciloleucel] is a second-line standard of care for patients with refractory or early relapsed large B-cell lymphoma based on superior survival,” summarized presenting author Jason Westin (University of Texas MD Anderson Cancer Center, Houston, USA).
He reminded delegates that the study’s primary endpoint of improved event-free survival (EFS) by central review with axi-cel was met after a median follow-up of 24.9 months.
The secondary endpoint of median OS, determined after a median 47.2 months, was not reached in the 180 patients who were randomly assigned to receive a single dose of axi-cel, to a target of 2x106 CAR T-cells/kg, after undergoing leukapheresis and a conditioning regimen of cyclophosphamide and fludarabine. Overall, 94% of the patients completed the planned treatment.
This OS was significantly longer than the median 31.1 months achieved by the 179 patients who instead received usual care consisting of 2–3 cycles of physician’s choice of platinum-based chemotherapy (such as the R-GDP or R-DHAP regimens). Just 36% of these patients achieved a complete or partial response to chemotherapy and were eligible to proceed to high-dose therapy with autologous stem cell transplantation (HDT–ASCT).
The risk of death was therefore a significant 27% lower with axi-cel than standard care. Overall, 54.6% and 46.0% of patients were alive at 4 years, respectively, prompting Westin to say that the “long-term survival curve plateaus [in ZUMA-7] are generally consistent with curative therapy.”
The presenter highlighted that axi-cel achieved the significant OS improvement despite the usual care arm having better survival than previously reported for the control regimen in the ORCHARRD trial, likely due to 57% of these participants going onto receive axi-cel or other types of cellular immunotherapy outside of the ZUMA-7 trial.
“This conclusively demonstrates that trying chemotherapy in the second line and saving cell therapy for third line is an inferior approach,” emphasized Westin, who recommended that clinicians now consider CAR T-cell therapy for patients with relapsed or refractory disease rather than HDT–ASCT.
The updated safety data indicated there were no new treatment-related serious or fatal adverse events (AEs). Progressive disease was the major cause of death in both the axi-cel and standard care treatment arms (30 vs 42%), followed by grade 5 AEs (1 vs 0%) and other causes (8 vs 11%).
Asher Chanan-Khan (Mayo Clinic Cancer Center, Jacksonville, Florida, USA) acted as session discussant and said that the ZUMA-7 findings “must alter the standard of care” for patients who have relapsed or refractory disease after initial treatment.
He suggested that future directions of research might include first-line use of CAR T-cell therapy for patients with high-risk or advanced disease, as well as exploring the possibility of repeating CAR T-cell therapy in some form for some patients.
medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2023 Springer Healthcare Ltd, part of the Springer Nature Group
2023 ASCO Annual Meeting; Chicago, Illinois, USA: 2–6 June
N Engl J Med 2023; doi: 10.1056/NEJMoa2301665