# ZUMA-2: brexu-cel CAR-T for mantle cell lymphoma that has failed BTK inhibitors

Source: https://onco.cc/key-papers/paper-zuma-2-brexu-cel-mantle-cell-nejm-2020/  
OnCo record `paper-zuma-2-brexu-cel-mantle-cell-nejm-2020` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

In mantle cell lymphoma that had stopped responding to BTK inhibitors, a single CAR-T infusion produced responses in 93% of patients and complete remissions in two-thirds.

## Summary

ZUMA-2 was a single-arm phase 2 study of KTE-X19 (brexucabtagene autoleucel), a CD19 CAR-T manufactured with removal of circulating tumour cells, in relapsed or refractory mantle cell lymphoma after up to five prior lines including a BTK inhibitor. Of 74 patients enrolled, 68 received the product. In the primary efficacy analysis of the first 60 treated patients the overall response rate was 93% and complete response 67%; estimated 12-month PFS was 61% and OS 83%. Grade 3 or higher CRS occurred in 15% and neurological events in 31%. It led to FDA approval in 2020, the first CAR-T for mantle cell lymphoma.

## Fields

- Kind: Key paper
- Last checked: 2026-09-08
- Journal: New England Journal of Medicine
- Year: 2020
- DOI: 10.1056/NEJMoa1914347
- Authors: Wang M, Munoz J, Goy A, et al.
- Findings: 74 enrolled, 68 treated; all had prior BTK inhibitor; 60 in primary efficacy analysis.; Overall response 93%; complete response 67%.; Estimated 12-month PFS 61%; 12-month OS 83%.; Grade 3 or higher CRS 15%; grade 3 or higher neurological events 31%.; Responses seen in high-risk features including TP53 mutation and blastoid morphology.
- What it means: ZUMA-2 gave patients with BTK-inhibitor-refractory mantle cell lymphoma, who previously had a median survival under a year, a therapy with durable remissions in a substantial fraction. Brexu-cel is now standard after BTK inhibitor failure and CAR-T is being tested earlier in the disease. Neurotoxicity rates are higher than in other lymphoma CAR-T trials.
- Caveats: Single-arm; no randomised comparison.; High rates of neurological toxicity, and a treatment-related death rate that requires experienced centres.; Later real-world data showed lower complete response rates than the trial.; Long-term durability is limited by late relapses in roughly half of responders.

## Sources

- Full text (DOI): https://doi.org/10.1056/NEJMoa1914347
- ClinicalTrials.gov NCT02601313: https://clinicaltrials.gov/study/NCT02601313

## Connected records

- key papers: [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/)
- cancers: [Mantle cell lymphoma](https://onco.cc/cancers/mantle-cell-lymphoma/)
- technologies: [CAR-T cell therapy](https://onco.cc/technologies/car-t/)
- targets: [BTK (Bruton tyrosine kinase)](https://onco.cc/targets/btk/), [CD19](https://onco.cc/targets/cd19/)
- drugs: [Brexucabtagene autoleucel](https://onco.cc/drugs/brexucabtagene-autoleucel/), [Ibrutinib](https://onco.cc/drugs/ibrutinib/), [Pirtobrutinib](https://onco.cc/drugs/pirtobrutinib/)
- companies: [Gilead Sciences (incl. Kite)](https://onco.cc/companies/gilead/)
- institutions: [MD Anderson Cancer Center](https://onco.cc/institutions/md-anderson/)
- terms: [Cytokine release syndrome (CRS)](https://onco.cc/terms/crs/), [ICANS (neurotoxicity)](https://onco.cc/terms/icans/), [Objective response rate (ORR)](https://onco.cc/terms/orr/)
- bottlenecks: [Acquired resistance to every therapy](https://onco.cc/bottlenecks/b-resistance/), [Toxicity and quality of life are undervalued](https://onco.cc/bottlenecks/b-toxicity-qol/)
- journals: [New England Journal of Medicine](https://onco.cc/journals/nejm/)
- people: [Michael L. Wang](https://onco.cc/people/michael-wang/)

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