# Maude 2014: CD19 CAR-T cells produce complete remission in 27 of 30 children and adults with relapsed ALL

Source: https://onco.cc/key-papers/paper-maude-ctl019-all-nejm-2014/  
OnCo record `paper-maude-ctl019-all-nejm-2014` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

The first sizeable series of CD19 CAR-T therapy showed complete remission in 90% of patients with leukaemia that had failed everything else, with persistent engineered cells and a new, treatable toxicity.

## Summary

Maude and colleagues reported 30 patients (25 children and 5 adults) with relapsed or refractory ALL, including 18 who had relapsed after allogeneic transplant and 3 refractory to blinatumomab, treated with CTL019, an autologous CD19-directed CAR-T with a 4-1BB costimulatory domain. Complete remission occurred in 27 (90%), including MRD-negative remissions; six-month event-free survival was 67% and overall survival 78%. CAR-T cells persisted for up to two years with ongoing B-cell aplasia. All patients developed cytokine release syndrome, severe in 27%, which was reversed by the IL-6 receptor antibody tocilizumab. Together with the earlier single-patient CLL report (Porter et al., NEJM 2011) and the first two children (Grupp et al., NEJM 2013), it established CAR-T as a realistic therapy and drove the pivotal ELIANA trial.

## Fields

- Kind: Key paper
- Last checked: 2026-09-08
- Journal: New England Journal of Medicine
- Year: 2014
- DOI: 10.1056/NEJMoa1407222
- Authors: Maude SL, Frey N, Shaw PA, et al.
- Findings: 30 patients (25 children, 5 adults) with relapsed/refractory ALL; 18 post-transplant, 3 blinatumomab-refractory.; Complete remission in 27 of 30 (90%); 22 of 27 MRD-negative by flow cytometry.; 6-month event-free survival 67%; overall survival 78%; 19 patients in sustained remission at report.; CAR-T persistence and B-cell aplasia for up to 2 years in responders.; CRS in 100%, severe in 27%; reversed with tocilizumab; CD19-negative relapse identified as an escape mechanism.
- What it means: This paper is the proof-of-concept for a living drug: a single infusion of a patient's own engineered T cells could eradicate leukaemia that had survived chemotherapy, transplant and antibody therapy. It defined cytokine release syndrome and its antidote, tocilizumab, and revealed antigen-loss relapse. It led directly to the first approved gene-modified cell therapy three years later.
- Caveats: Single-centre, uncontrolled series with short follow-up.; Selected patients able to wait for manufacturing and tolerate lymphodepletion.; Durability was uncertain; about a third relapsed within months, often with CD19-negative disease.; Toxicity management was still empirical.

## Sources

- Full text (DOI): https://doi.org/10.1056/NEJMoa1407222
- First CLL patient report (Porter 2011): https://doi.org/10.1056/NEJMoa1103849
- ClinicalTrials.gov NCT01626495: https://clinicaltrials.gov/study/NCT01626495

## Connected records

- key papers: [ELIANA: the global trial that made tisagenlecleucel the first approved CAR-T therapy for children and young adults with relapsed ALL](https://onco.cc/key-papers/paper-eliana-tisagenlecleucel-nejm-2018/)
- cancers: [Acute lymphoblastic leukaemia](https://onco.cc/cancers/all-leukemia/), [Chronic lymphocytic leukaemia](https://onco.cc/cancers/cll/)
- technologies: [CAR-T cell therapy](https://onco.cc/technologies/car-t/)
- targets: [CD19](https://onco.cc/targets/cd19/)
- drugs: [Tisagenlecleucel](https://onco.cc/drugs/tisagenlecleucel/)
- companies: [Novartis](https://onco.cc/companies/novartis/)
- institutions: [Abramson Cancer Center, University of Pennsylvania](https://onco.cc/institutions/penn-abramson/)
- terms: [Cytokine release syndrome (CRS)](https://onco.cc/terms/crs/), [MRD-negative complete remission](https://onco.cc/terms/mrd-negative-cr/)
- people: [Bruce L. Levine](https://onco.cc/people/bruce-levine/), [Carl H. June](https://onco.cc/people/carl-june/), [David L. Porter](https://onco.cc/people/david-porter/), [Stephan A. Grupp](https://onco.cc/people/stephan-grupp/)
- bottlenecks: [Manufacturing cost and time for living and radioactive medicines](https://onco.cc/bottlenecks/b-manufacturing-cell-therapy/), [The valley of death between lab and product](https://onco.cc/bottlenecks/b-translational-valley/)
- journals: [New England Journal of Medicine](https://onco.cc/journals/nejm/)

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