ZUMA-7
A Phase 3, Randomized, Open-Label Study Evaluating the Efficacy of Axicabtagene Ciloleucel Versus Standard of Care Therapy in Subjects With Relapsed/Refractory Diffuse Large B Cell Lymphoma (ZUMA-7)
Phase 3N = 359NCT03391466
- Population
- Adults with large B-cell lymphoma refractory to, or relapsed within 12 months of, first-line chemoimmunotherapy.
- Design
- International phase 3 trial: 359 patients with large B-cell lymphoma refractory to, or relapsing no more than 12 months after, first-line chemoimmunotherapy were randomised 1:1 to axi-cel or standard care (two or three cycles of investigator-selected, protocol-defined chemoimmunotherapy followed by high-dose chemotherapy with autologous stem-cell transplantation in responders). Primary end point: event-free survival by blinded central review; key secondary end points: response and overall survival.
- Primary endpoint
- EFS
- Arms
- Standard care (control, n = 179): Two or three cycles of investigator-selected, protocol-defined chemoimmunotherapy, then high-dose chemotherapy with autologous stem-cell transplantation in patients with a response
- Axicabtagene ciloleucel (experimental, n = 180): Autologous anti-CD19 CAR T-cell therapy (axi-cel)
- People
- Locke FL, senior author Westin JR
EFSHR 0.40 (95% CI 0.31–0.51)Δ median EFS+6.3 monthsΔ 24-month EFS+25 pointsΔ Response rate+33 pointsΔ 24-month OS+9 pointsOSHR 0.73 (95% CI 0.54–0.98)
Show the numbers
| Endpoint | Analysis | Axicabtagene ciloleucel | Standard care | Effect |
|---|---|---|---|---|
| EFSAll randomised patients (359); the abstract does not use the label ITT for this analysisEvent-free survival according to blinded central review (stated primary end point). | primarymedian follow-up 24.9 monthsLocke 2022 | median 8.3 months; 41% at 2 y | median 2 months; 16% at 2 y | HR 0.40 (95% CI 0.31–0.51)P<0.001Hazard ratio for event or death. 24-month event-free survival rates shown as landmarks. |
| Response rateAll randomised patients (359); the abstract does not state the denominatorProportion of patients with a response, as reported (key secondary end point); the abstract gives no further definition. | primarymedian follow-up 24.9 monthsLocke 2022 | 83% | 50% | Complete response in 32% of the standard-care group and 65% of the axi-cel group. |
| OSAll randomised patients (359); the abstract does not use the label ITT for this analysis | interimLocke 2022 | 61% at 2 y | 52% at 2 y | Estimated overall survival at 2 years in an interim analysis. |
| OSPrespecified overall survival analysis at 5 years after the first patient was randomised. | long term-updatemedian follow-up 47.2 monthsWestin 2023 | 54.6% at 4 y | median 31.1 months; 46% at 4 y | HR 0.73 (95% CI 0.54–0.98)P=0.03Median overall survival not reached in the axi-cel group. Deaths: 82 in the axi-cel group and 95 in the standard-care group. Stratified two-sided log-rank test. 74% of patients had primary refractory disease and other high-risk features. |
| PFSInvestigator-assessed progression-free survival. | long term-updatemedian follow-up 47.2 monthsWestin 2023 | median 14.7 months; 41.8% at 4 y | median 3.7 months; 24.4% at 4 y | HR 0.51 (95% CI 0.38–0.67) |
| Endpoint | Analysis | Axicabtagene ciloleucel | Standard care | Effect |
|---|---|---|---|---|
| EFSAll randomised patients (359); the abstract does not use the label ITT for this analysisEvent-free survival according to blinded central review (stated primary end point). | primarymedian follow-up 24.9 monthsLocke 2022 | median 8.3 months; 41% at 2 y | median 2 months; 16% at 2 y | HR 0.40 (95% CI 0.31–0.51)P<0.001Hazard ratio for event or death. 24-month event-free survival rates shown as landmarks. |
| Response rateAll randomised patients (359); the abstract does not state the denominatorProportion of patients with a response, as reported (key secondary end point); the abstract gives no further definition. | primarymedian follow-up 24.9 monthsLocke 2022 | 83% | 50% | Complete response in 32% of the standard-care group and 65% of the axi-cel group. |
| OSAll randomised patients (359); the abstract does not use the label ITT for this analysis | interimLocke 2022 | 61% at 2 y | 52% at 2 y | Estimated overall survival at 2 years in an interim analysis. |
| OSPrespecified overall survival analysis at 5 years after the first patient was randomised. | long term-updatemedian follow-up 47.2 monthsWestin 2023 | 54.6% at 4 y | median 31.1 months; 46% at 4 y | HR 0.73 (95% CI 0.54–0.98)P=0.03Median overall survival not reached in the axi-cel group. Deaths: 82 in the axi-cel group and 95 in the standard-care group. Stratified two-sided log-rank test. 74% of patients had primary refractory disease and other high-risk features. |
| PFSInvestigator-assessed progression-free survival. | long term-updatemedian follow-up 47.2 monthsWestin 2023 | median 14.7 months; 41.8% at 4 y | median 3.7 months; 24.4% at 4 y | HR 0.51 (95% CI 0.38–0.67) |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| EFS | 0.4 | 0.31–0.51 |
| OS | 0.73 | 0.54–0.98 |
| PFS | 0.51 | 0.38–0.67 |
- Standard care (control)
- Axicabtagene ciloleucel (experimental)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Standard care | Axicabtagene ciloleucel |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 5 | 17.7% | 65.9% |
| 10 | 3.1% | 43.4% |
| 16 | 0.4% | 26.3% |
| 21 | 0.1% | 17.3% |
- Standard care (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Standard care |
|---|---|
| 0 | 100.0% |
| 19 | 65.5% |
| 39 | 41.9% |
| 58 | 27.5% |
| 78 | 17.6% |
Appears in
Sources
Locke FL, Miklos DB, Jacobson CA, Perales MA, Kersten MJ, Oluwole OO, et al. Axicabtagene Ciloleucel as Second-Line Therapy for Large B-Cell Lymphoma. N Engl J Med. 2022;386(7):640-654.
Westin JR, Oluwole OO, Kersten MJ, Miklos DB, Perales MA, Ghobadi A, et al. Survival with Axicabtagene Ciloleucel in Large B-Cell Lymphoma. N Engl J Med. 2023;389(2):148-157.