Author: By Lynda Williams, Senior medwireNews Reporter
medwireNews: ZUMA-7 trial findings demonstrate a significant event-free survival (EFS) benefit for patients with large B-cell lymphoma given second-line therapy with axicabtagene ciloleucel (axi-cel) compared with standard care.
The research was presented at the 63rd American Society of Hematology Annual Meeting & Exposition in Atlanta, Georgia, USA, and simultaneously reported in The New England Journal of Medicine.
“Axi-cel appears to be a viable alternative to a regimen of chemoimmunotherapy, high-dose chemotherapy, and autologous stem-cell transplantation for the second-line treatment of relapsed or refractory large B-cell lymphoma”, say Frederick Locke, from Moffitt Cancer Center in Tampa, Florida, USA, and co-authors.
For the phase III trial, patients who had relapsed within 12 months of first-line chemoimmunotherapy or had refractory disease were randomly assigned to receive either the autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy axi-cel or standard care with 2–3 cycles of protocol-specified chemoimmunotherapy. Patients responding to chemoimmunotherapy were then scheduled to receive high-dose chemotherapy and autologous stem-cell transplantation.
Overall, 170 of the 180 patients in the axi-cel group received their CAR T-cell infusion. Of the 179 patients in the standard care arm, 168 received at least one dose of salvage chemotherapy and 80 responded to the treatment; 69 underwent leukapheresis, 64 received high-dose chemotherapy and 62 underwent CD34+ stem-cell therapy.
After a median 24.9 months of follow-up, the primary endpoint of median EFS was 8.3 months for the patients who were randomly assigned to receive axi-cel versus 2.0 months with standard care. The 24-month rate of EFS was significantly higher with axi-cel than standard care, with a hazard ratio (HR) for event or death of 0.40.
In addition, 83% of the axi-cel group responded to treatment compared with 50% of the standard care group, with complete responses reported in 65% and 32% of patients, respectively.
Median progression-free survival was significantly longer with axi-cel than standard care, at 14.7 versus 3.7 months and a HR of 0.47. The 2-year rates were 46% and 27%, respectively.
Interim analysis showed that median overall survival (OS) was unreached with axi-cel and 35.1 months with standard care, with a HR for death of 0.73 that did not reach statistical significance. The 2-year rates of OS were 61% and 52%, respectively, with progressive disease-related deaths occurring in a corresponding 29% and 36% of the treatment arms.
The researchers note that the OS analysis may have been confounded by the use of CAR T-cell therapy outside of the study protocol by 56% of the standard care arm who had not responded to treatment or experienced progressive disease.
“The median overall survival in the standard-care group was longer than has been observed in historical studies”, they add, writing that “this finding is potentially due to the availability of newer agents, such as CAR T-cell therapy, that can be used in patients whose disease is refractory to or relapses after second-line therapy.”
Frederick Locke et al also highlight that 30% of patients in the ZUMA-7 study were aged at least 65 years, showing that “axi-cel can be an effective second-line therapeutic option in elderly patients who do not have clinically significant coexisting conditions.”
Grade 3 and more severe adverse events (AEs) occurred in 91% of the axi-cel arm and 83% of the standard care am, including infection in 14% versus 11%, and serious AEs of any grade were reported for 50% versus 46%.
Grade 3 or more severe neurological events occurred in 21% of patients given axi-cel and 1% of controls, after a median of 7 and 23 days, respectively, with no related deaths.
Among patients given axi-cel, 92% experienced cytokine release syndrome (CRS) a median of 3 days after infusion and 6% had grade 3 or more severe CRS; 65% received tocilizumab, 24% glucocorticoids and 6% vasopressors, and there were no CRS-related deaths.
Frederick Locke et al summarise: “Treatment with axi-cel induced high-grade adverse events in the vast majority of patients, but few patients had fatal effects from treatment and the magnitude of the toxicity was consistent with previous reports in third-line therapy, although unique problems attend CAR T-cell therapy.”
Locke FL, Miklos DB, Jacobson CA, et al. Axicabtagene ciloleucel as second-line therapy for large B-cell lymphoma. N Engl J Med; Advance online publication 11 December 2021. Doi: 10.1056/NEJMoa2116133
Locke FL, Miklos DB, Jacobson CA, et al. Primary Analysis of ZUMA7: A Phase 3 Randomized Trial of Axicabtagene Ciloleucel (Axi-Cel) Versus StandardofCare Therapy in Patients with Relapsed/Refractory Large B-Cell Lymphoma. Abstract 2. 63rd American Society of Hematology Annual Meeting & Exposition; Atlanta, Georgia, USA: 11–14 December 2021
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