The ZUMA-7 study was a global randomised phase III trial evaluating axicabtagene ciloleucel, or axi-cel, a CD19 targeting CAR T-cell therapy, compared with the old standard of care which was platinum-based chemotherapy followed by high dose therapy and autologous transplant in patients in second-line large B-cell lymphoma. The trial enrolled a large number of patients, 359 patients, randomised 1:1, and the primary endpoint of this study was event free survival. We presented that last year in The New England Journal of Medicine, showing axi-cel has statistically significant improvement in event free survival. This year at the ASCO 2023 meeting we presented the primary overall survival analysis where we showed that axi-cel has a statistically significantly improved overall survival of the CAR T cell therapy over the chemotherapy-based previous paradigm.
The study design of the ZUMA-7 trial was enrolling patients with refractory second-line large B-cell lymphoma, or patients who had relapsed within 12 months of their first-line treatment. We know historically from previous studies that patients treated with chemotherapy in that setting where they had not received a long-term benefit from first-line chemotherapy, had poor outcomes. So this was a high-risk patient subset. On the ZUMA-7 trial, 75% of patients were refractory to first-line therapy which, generally speaking, bodes poorly for their outcomes. As expected, the chemotherapy standard of care arm had lower response rates, lower progression free and overall survival compared to the axi-cel arm. That’s why we believe axi-cel should be a new standard of care.
How might these results impact clinical practice?
The results of the ZUMA-7 clinical trial will have a direct impact on clinical practice starting very soon. The previous paradigm for nearly the past 30 years was to try chemotherapy first, to try to go to autologous transplant, and if that didn’t work, outcomes were generally quite poor. With the approval of CAR T cells in the third-line setting, about five or six years ago, we had a new option which could help a subset of patients, but on the ZUMA-7 clinical trial we found that trying chemo first and saving CAR T cell therapy for a third-line approach was inferior to using axi-cel or CAR T cell as a second-line treatment. The practice implications for our findings are that, effectively, axi-cel as a second-line treatment would be preferred over trying chemo and saving cell therapy for a later day.