Dataset Information

Treatment of adult ALL patients with third-generation CD19-directed CAR T cells: results of a pivotal trial.

ABSTRACT:

Background

Third-generation chimeric antigen receptor (CAR)-engineered T cells (CARTs) might improve clinical outcome of patients with B cell malignancies. This is the first report on a third-generation CART dose-escalating, phase-1/2 investigator-initiated trial treating adult patients with refractory and/or relapsed (r/r) acute lymphoblastic leukemia (ALL).

Methods

Thirteen patients were treated with escalating doses of CD19-directed CARTs between 1 × 10⁶ and 50 × 10⁶ CARTs/m². Leukapheresis, manufacturing and administration of CARTs were performed in-house.

Results

For all patients, CART manufacturing was feasible. None of the patients developed any grade of Immune effector cell-associated neurotoxicity syndrome (ICANS) or a higher-grade (≥ grade III) catokine release syndrome (CRS). CART expansion and long-term CART persistence were evident in the peripheral blood (PB) of evaluable patients. At end of study on day 90 after CARTs, ten patients were evaluable for response: Eight patients (80%) achieved a complete remission (CR), including five patients (50%) with minimal residual disease (MRD)-negative CR. Response and outcome were associated with the administered CART dose. At 1-year follow-up, median overall survival was not reached and progression-free survival (PFS) was 38%. Median PFS was reached on day 120. Lack of CD39-expression on memory-like T cells was more frequent in CART products of responders when compared to CART products of non-responders. After CART administration, higher CD8 + and γδ-T cell frequencies, a physiological pattern of immune cells and lower monocyte counts in the PB were associated with response.

Conclusion

In conclusion, third-generation CARTs were associated with promising clinical efficacy and remarkably low procedure-specific toxicity, thereby opening new therapeutic perspectives for patients with r/r ALL. Trial registration This trial was registered at www.

Clinicaltrials

gov as NCT03676504.

SUBMITTER: Schubert ML

PROVIDER: S-EPMC10363324 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature

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Publications

Treatment of adult ALL patients with third-generation CD19-directed CAR T cells: results of a pivotal trial.

Schubert Maria-Luisa ML Schmitt Anita A Hückelhoven-Krauss Angela A Neuber Brigitte B Kunz Alexander A Waldhoff Philip P Vonficht Dominik D Yousefian Schayan S Jopp-Saile Lea L Wang Lei L Korell Felix F Keib Anna A Michels Birgit B Haas Dominik D Sauer Tim T Derigs Patrick P Kulozik Andreas A Kunz Joachim J Pavel Petra P Laier Sascha S Wuchter Patrick P Schmier Johann J Bug Gesine G Lang Fabian F Gökbuget Nicola N Casper Jochen J Görner Martin M Finke Jürgen J Neubauer Andreas A Ringhoffer Mark M Wolleschak Denise D Brüggemann Monika M Haas Simon S Ho Anthony D AD Müller-Tidow Carsten C Dreger Peter P Schmitt Michael M

Journal of hematology & oncology 20230722 1

<h4>Background</h4>Third-generation chimeric antigen receptor (CAR)-engineered T cells (CARTs) might improve clinical outcome of patients with B cell malignancies. This is the first report on a third-generation CART dose-escalating, phase-1/2 investigator-initiated trial treating adult patients with refractory and/or relapsed (r/r) acute lymphoblastic leukemia (ALL).<h4>Methods</h4>Thirteen patients were treated with escalating doses of CD19-directed CARTs between 1 × 10<sup>6</sup> and 50 × 10< ...[more]

PMID: 37481608

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Project description:IntroductionEEG patterns in chimeric antigen receptor T cell treatment-associated neurotoxicity (immune effector cell-associated neurotoxicity syndrome) have not yet been systematically studied. We tested the hypothesis that EEG background abnormalities in immune effector cell-associated neurotoxicity syndrome correlate with clinical signs of neurotoxicity. In addition, we describe ictal and interictal EEG patterns to better understand the natural history of immune effector cell-associated neurotoxicity syndrome-associated seizures.MethodsEEGs were obtained in 19 of 100 subjects in a prospective cohort study of children and young adults undergoing CD19-directed chimeric antigen receptor T cell therapy. We classified the EEG background on a severity scale of 0 to 5 during 30-minute epochs. EEG grades were compared with neurotoxicity scored by Common Terminology Criteria for Adverse Events and Cornell Assessment of Pediatric Delirium scores. Descriptive analysis was conducted for ictal and interictal EEG abnormalities.ResultsEEG background abnormality scores correlated well with Common Terminology Criteria for Adverse Events neurotoxicity scores (P = 0.0022) and Cornell Assessment of Pediatric Delirium scores (P = 0.0085). EEG was better able to differentiate the severity of coma patterns compared with the clinical scores. The EEG captured electroclinical seizures in 4 of 19 subjects, 3 of whom had additional electrographic-only seizures. Seizures most often arose from posterior head regions. Interictal epileptiform discharges were focal, multifocal, or lateralized periodic discharges. No seizures or interictal epileptiform abnormalities were seen in subjects without previous clinical seizures.ConclusionsContinuous EEG monitoring is high yield for seizure detection in high-risk chimeric antigen receptor T cell patients, and electrographic-only seizures are common. Increasing severity of EEG background abnormalities correlates with increasing neurotoxicity grade.

Dataset Information

Treatment of adult ALL patients with third-generation CD19-directed CAR T cells: results of a pivotal trial.

Background

Methods

Results

Conclusion

Clinicaltrials

Publications

Treatment of adult ALL patients with third-generation CD19-directed CAR T cells: results of a pivotal trial.

Similar Datasets

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