# Axicabtagene ciloleucel in relapsed or refractory indolent non-Hodgkin lymphoma (ZUMA-5): a single-arm, multicentre, phase 2 trial

Source: https://onco.cc/key-papers/paper-zuma-5-axi-cel-indolent-lymphoma-lancet-oncol-2022/  
OnCo record `paper-zuma-5-axi-cel-indolent-lymphoma-lancet-oncol-2022` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

The first CAR-T trial in slow-growing lymphoma: more than nine in ten responded and three quarters went into complete remission, with severe neurological events in about one in five.

## Summary

A single-arm phase 2 trial at 15 centres in the United States and two in France, in patients aged 18 or over with relapsed or refractory follicular lymphoma or marginal zone lymphoma who had received two or more previous lines including an anti-CD20 antibody with an alkylating agent. Patients had conditioning chemotherapy with cyclophosphamide 500 mg per square metre and fludarabine 30 mg per square metre on days minus 5, minus 4 and minus 3, then a single infusion of axicabtagene ciloleucel at 2 million chimeric antigen receptor T cells per kilogram.

Between 20 June 2017 and 16 July 2020, 153 patients were enrolled and axicabtagene ciloleucel was successfully manufactured for all of them; 148 were infused, 124 with follicular lymphoma and 24 with marginal zone lymphoma. Among the 104 patients eligible for the primary analysis, 96 (92 per cent, 95 per cent confidence interval 85 to 97) had an overall response and 77 (74 per cent) a complete response, at a median follow-up of 17.5 months.

## Fields

- Kind: Key paper
- Last checked: 2026-10-01
- Also known as: ZUMA-5; Jacobson 2022
- Tags: lymphoma-evidence
- Journal: Lancet Oncology
- Year: 2022
- DOI: 10.1016/S1470-2045(21)00591-X
- Authors: Jacobson CA, Chavez JC, Sehgal AR, et al.
- Findings: Of 104 patients in the primary analysis, 96 (92 per cent, 95 per cent confidence interval 85 to 97) had an overall response and 77 (74 per cent) a complete response.; Axicabtagene ciloleucel was successfully manufactured for all 153 enrolled patients.; Grade 3 or worse cytokine release syndrome occurred in ten patients (7 per cent) and grade 3 or 4 neurological events in 28 (19 per cent).; The most common grade 3 or worse adverse events were cytopenias in 104 patients (70 per cent) and infections in 26 (18 per cent).; Deaths due to adverse events occurred in four patients (3 per cent), one deemed treatment-related.
- What it means: Axicabtagene ciloleucel as an option in relapsed follicular and marginal zone lymphoma. Compared with tisagenlecleucel in ELARA, the response rates are higher and the neurological toxicity substantially greater, which is the trade-off a patient and centre weigh.
- Caveats: Single-arm, so the comparison with ELARA is cross-trial, with different eligibility and different follow-up.; Only 24 patients had marginal zone lymphoma, so the result in that disease rests on very small numbers.; Grade 3 or 4 neurological events in 19 per cent require a centre equipped to manage them.; Median follow-up of 17.5 months in a disease measured in decades.

## Sources

- Lancet Oncology 2022: https://doi.org/10.1016/S1470-2045(21)00591-X
- PubMed: https://pubmed.ncbi.nlm.nih.gov/34895487/
- Europe PMC: https://europepmc.org/article/MED/34895487

## Connected records

- 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/)
- cancers: [Follicular lymphoma](https://onco.cc/cancers/follicular-lymphoma/), [Marginal zone lymphoma](https://onco.cc/cancers/marginal-zone-lymphoma/), [Non-Hodgkin lymphoma (all types)](https://onco.cc/cancers/non-hodgkin-lymphoma/)
- fronts: [Cell Therapy](https://onco.cc/fronts/cell-therapy/)
- technologies: [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/), [Cyclophosphamide](https://onco.cc/drugs/cyclophosphamide/), [Fludarabine](https://onco.cc/drugs/fludarabine/)
- companies: [Gilead Sciences (incl. Kite)](https://onco.cc/companies/gilead/)
- terms: [Cytokine release syndrome (CRS)](https://onco.cc/terms/crs/), [ICANS (neurotoxicity)](https://onco.cc/terms/icans/), [Lugano classification / Ann Arbor staging](https://onco.cc/terms/lugano-classification/), [Lymphodepletion before CAR-T](https://onco.cc/terms/lymphodepletion/)
- trials: [ELARA](https://onco.cc/trials/elara/), [ZUMA-5](https://onco.cc/trials/zuma-5/)
- people: [Caron A. Jacobson](https://onco.cc/people/caron-jacobson/), [Gilles Salles](https://onco.cc/people/gilles-salles/)
- bottlenecks: [Manufacturing cost and time for living and radioactive medicines](https://onco.cc/bottlenecks/b-manufacturing-cell-therapy/), [Toxicity and quality of life are undervalued](https://onco.cc/bottlenecks/b-toxicity-qol/)
- journals: [The Lancet Oncology](https://onco.cc/journals/lancet-oncology/)

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