ZUMA-5
Axicabtagene ciloleucel in relapsed or refractory indolent non-Hodgkin lymphoma (ZUMA-5): a single-arm, multicentre, phase 2 trial
Phase 2N = 153NCT03105336
- Population
- Relapsed or refractory indolent non-Hodgkin lymphoma (follicular or marginal zone) after two or more lines of therapy. Primary analysis population: 104 eligible patients (84 follicular, 20 marginal zone). Three-year report: 127 follicular and 31 marginal zone lymphoma patients.
- Design
- Single-arm, multicentre phase 2 trial at 15 centres in the USA and 2 in France of axicabtagene ciloleucel (single infusion of 2 x 10^6 CAR T cells per kg after fludarabine and cyclophosphamide conditioning) in adults with relapsed or refractory follicular or marginal zone lymphoma after two or more lines of therapy including an anti-CD20 antibody and an alkylating agent. Primary endpoint: overall response rate by independent review per Lugano classification, in the per-protocol population. 153 patients were enrolled and 148 were infused (124 with follicular lymphoma and 24 with marginal zone lymphoma).
- Primary endpoint
- ORR
- Arms
- Axicabtagene ciloleucel (experimental, n = 148): Single infusion of 2 x 10^6 CAR T cells per kg after fludarabine and cyclophosphamide conditioning
- People
- Jacobson CA
Show the numbers
| Endpoint | Analysis | Axicabtagene ciloleucel | Control | Effect |
|---|---|---|---|---|
| ORRPer-protocol primary analysis set: 104 eligible patients (84 follicular, 20 marginal zone lymphoma) | primarymedian follow-up 17.5 monthsJacobson 2022 | 92% (85–97%) | — | 96 of 104 patients responded. The abstract does not give a response rate for the follicular subset in this analysis. |
| CR ratePer-protocol primary analysis set: 104 eligible patients (84 follicular, 20 marginal zone lymphoma) | primarymedian follow-up 17.5 monthsJacobson 2022 | 74% | — | 77 of 104 patients had a complete response; the abstract gives no confidence interval. |
| ORRFollicular lymphoma, all enrolled patients (intent-to-treat; n=127), investigator-assessed | long term-updatemedian follow-up 41.7 monthsNeelapu 2024 | 94% | — | Three-year follow-up report. Marginal zone lymphoma ORR 77% (n=31, median follow-up 31.8 months). |
| PFSFollicular lymphoma, all enrolled patients (intent-to-treat; n=127), investigator-assessed | long term-updatemedian follow-up 41.7 monthsNeelapu 2024 | median 40.2 months | — | Median overall survival was not reached in either disease type. |
| Endpoint | Analysis | Axicabtagene ciloleucel | Control | Effect |
|---|---|---|---|---|
| ORRPer-protocol primary analysis set: 104 eligible patients (84 follicular, 20 marginal zone lymphoma) | primarymedian follow-up 17.5 monthsJacobson 2022 | 92% (85–97%) | — | 96 of 104 patients responded. The abstract does not give a response rate for the follicular subset in this analysis. |
| CR ratePer-protocol primary analysis set: 104 eligible patients (84 follicular, 20 marginal zone lymphoma) | primarymedian follow-up 17.5 monthsJacobson 2022 | 74% | — | 77 of 104 patients had a complete response; the abstract gives no confidence interval. |
| ORRFollicular lymphoma, all enrolled patients (intent-to-treat; n=127), investigator-assessed | long term-updatemedian follow-up 41.7 monthsNeelapu 2024 | 94% | — | Three-year follow-up report. Marginal zone lymphoma ORR 77% (n=31, median follow-up 31.8 months). |
| PFSFollicular lymphoma, all enrolled patients (intent-to-treat; n=127), investigator-assessed | long term-updatemedian follow-up 41.7 monthsNeelapu 2024 | median 40.2 months | — | Median overall survival was not reached in either disease type. |
- 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 | Axicabtagene ciloleucel |
|---|---|
| 0 | 100.0% |
| 25 | 65.0% |
| 50 | 42.2% |
| 75 | 27.4% |
| 101 | 17.5% |
Appears in
Sources
Jacobson CA, Chavez JC, Sehgal AR, William BM, Munoz J, Salles G, et al. Axicabtagene ciloleucel in relapsed or refractory indolent non-Hodgkin lymphoma (ZUMA-5): a single-arm, multicentre, phase 2 trial. Lancet Oncol. 2022;23(1):91-103.
Neelapu SS, Chavez JC, Sehgal AR, Epperla N, Ulrickson M, Bachy E, et al. Three-year follow-up analysis of axicabtagene ciloleucel in relapsed/refractory indolent non-Hodgkin lymphoma (ZUMA-5). Blood. 2024;143(6):496-506.