# ZUMA-7: axi-cel CAR-T instead of salvage chemotherapy and transplant for large B-cell lymphoma that relapses early

Source: https://onco.cc/key-papers/paper-zuma-7-axi-cel-second-line-nejm-2022/  
OnCo record `paper-zuma-7-axi-cel-second-line-nejm-2022` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

For lymphoma that came back within a year, going straight to CAR-T beat the decades-old chemotherapy-then-transplant approach, and later improved survival.

## Summary

ZUMA-7 randomised 359 patients with large B-cell lymphoma that was refractory to, or relapsed within 12 months of, first-line chemo-immunotherapy to axicabtagene ciloleucel (axi-cel) or standard second-line salvage chemotherapy followed by high-dose therapy and autologous transplant in responders. The primary endpoint was event-free survival. Median EFS was 8.3 versus 2.0 months (hazard ratio 0.40) and 24-month EFS 41% versus 16%; complete response was 65% versus 32%. Only about a third of standard-arm patients reached transplant, and 56% went on to receive CAR-T off protocol. Despite that crossover, the later analysis (Westin et al., NEJM 2023) showed improved overall survival with axi-cel (4-year OS 54.6% versus 46.0%; hazard ratio 0.73).

## Fields

- Kind: Key paper
- Last checked: 2026-09-08
- Journal: New England Journal of Medicine
- Year: 2022
- DOI: 10.1056/NEJMoa2116133
- Authors: Locke FL, Miklos DB, Jacobson CA, et al.
- Findings: 359 patients with primary refractory or early-relapsing (within 12 months) LBCL; axi-cel vs salvage chemotherapy plus autologous transplant.; Median EFS 8.3 vs 2.0 months; hazard ratio 0.40; 24-month EFS 41% vs 16%.; Overall response 83% vs 50%; complete response 65% vs 32%.; Only 36% of standard-arm patients proceeded to transplant; 56% later received cellular therapy off protocol.; Overall survival improved (4-year OS 54.6% vs 46.0%; HR 0.73), the first survival gain in this setting in decades.; Grade 3 or higher CRS 6%; grade 3 or higher neurological events 21%; no bridging chemotherapy allowed (steroids only).
- What it means: ZUMA-7 rewrote second-line treatment for aggressive lymphoma: patients whose disease returns within a year of R-CHOP should be offered CAR-T rather than salvage chemotherapy and transplant. It is also one of the few cell-therapy trials to show an overall survival benefit despite crossover. Patients relapsing later than 12 months were not studied and transplant remains standard for them if chemosensitive.
- Caveats: Applies only to early relapse or primary refractory disease; late relapse was excluded.; No bridging chemotherapy was permitted, so patients with rapidly progressive disease may not have been enrolled.; The parallel BELINDA trial of tisagenlecleucel in the same setting was negative, showing the result depends on product and logistics.; Costs and centre capacity limit uptake outside high-income countries.

## Sources

- Full text (DOI): https://doi.org/10.1056/NEJMoa2116133
- Overall survival analysis (Westin 2023): https://doi.org/10.1056/NEJMoa2301665
- ClinicalTrials.gov NCT03391466: https://clinicaltrials.gov/study/NCT03391466

## Connected records

- pairings: [Early relapse: CAR-T before transplant](https://onco.cc/pairings/car-t-before-transplant-lbcl/)
- key papers: [Second-line tisagenlecleucel or standard care in aggressive B-cell lymphoma](https://onco.cc/key-papers/paper-belinda-tisagenlecleucel-second-line-nejm-2022/), [TRANSFORM: liso-cel CAR-T versus salvage chemotherapy and transplant in early-relapsing large B-cell lymphoma](https://onco.cc/key-papers/paper-transform-liso-cel-lancet-2022/), [ZUMA-1: axicabtagene ciloleucel for refractory large B-cell lymphoma, the first CAR-T approved for lymphoma](https://onco.cc/key-papers/paper-zuma-1-axi-cel-nejm-2017/)
- roadmaps: [Lymphoma roadmap: from a jaw tumour in Uganda and the first human cancer virus to gene-expression subtypes, PET-adapted chemotherapy, CAR-T cells, bispecific antibodies and the genetics-directed trials now recruiting](https://onco.cc/roadmaps/lymphoma-roadmap/)
- ideas: [Report the time from apheresis to infusion as a trial endpoint, not a logistics footnote](https://onco.cc/ideas/lymphoma-ev-manufacturing-time-as-a-trial-endpoint/)
- cancers: [Diffuse large B-cell lymphoma](https://onco.cc/cancers/dlbcl/)
- technologies: [Autologous stem cell transplant (high-dose therapy)](https://onco.cc/technologies/autologous-stem-cell-transplant/), [CAR-T cell therapy](https://onco.cc/technologies/car-t/)
- targets: [CD19](https://onco.cc/targets/cd19/)
- drugs: [Axicabtagene ciloleucel](https://onco.cc/drugs/axicabtagene-ciloleucel/)
- companies: [Gilead Sciences (incl. Kite)](https://onco.cc/companies/gilead/)
- institutions: [Moffitt Cancer Center](https://onco.cc/institutions/moffitt/)
- terms: [Cytokine release syndrome (CRS)](https://onco.cc/terms/crs/), [Event-free / disease-free survival (EFS, DFS, iDFS, RFS)](https://onco.cc/terms/efs/), [ICANS (neurotoxicity)](https://onco.cc/terms/icans/), [Overall survival (OS)](https://onco.cc/terms/os/)
- trials: [BELINDA](https://onco.cc/trials/belinda/), [TRANSFORM](https://onco.cc/trials/transform/), [ZUMA-7](https://onco.cc/trials/zuma-7/)
- people: [Frederick L. Locke](https://onco.cc/people/frederick-locke/), [Jason R. Westin](https://onco.cc/people/jason-westin/)
- bottlenecks: [Manufacturing cost and time for living and radioactive medicines](https://onco.cc/bottlenecks/b-manufacturing-cell-therapy/), [Most of the world has almost no cancer care](https://onco.cc/bottlenecks/b-global-access/)
- journals: [New England Journal of Medicine](https://onco.cc/journals/nejm/)

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