Schayan Yousefian - Treatment of adult ALL patients with

Journal article

M. Schubert, A. Schmitt, Angela Hückelhoven-Krauss, Brigitte Neuber, Alexander Kunz, Philipp Waldhoff, Dominik Vonficht, S. Yousefian, L. Jopp-Saile, Lei Wang, Felix Korell, Anna Keib, Birgit Michels, Dominik Haas, T. Sauer, P. Derigs, A. Kulozik, J. Kunz, P. Pavel, Sascha Laier, P. Wuchter, J. Schmier, G. Bug, F. Lang, N. Gökbuget, J. Casper, M. Görner, J. Finke, A. Neubauer, M. Ringhoffer, D. Wolleschak, M. Brüggemann, S. Haas, A. D. Ho, C. Müller-Tidow, P. Dreger, M. Schmitt
Journal of Hematology & Oncology, 2023

Semantic Scholar DOI PubMedCentral PubMed

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APA Click to copy
Schubert, M., Schmitt, A., Hückelhoven-Krauss, A., Neuber, B., Kunz, A., Waldhoff, P., … Schmitt, M. (2023). Treatment of adult ALL patients with third-generation CD19-directed CAR T cells: results of a pivotal trial. Journal of Hematology &Amp; Oncology.

Chicago/Turabian Click to copy
Schubert, M., A. Schmitt, Angela Hückelhoven-Krauss, Brigitte Neuber, Alexander Kunz, Philipp Waldhoff, Dominik Vonficht, et al. “Treatment of Adult ALL Patients with Third-Generation CD19-Directed CAR T Cells: Results of a Pivotal Trial.” Journal of Hematology & Oncology (2023).

MLA Click to copy
Schubert, M., et al. “Treatment of Adult ALL Patients with Third-Generation CD19-Directed CAR T Cells: Results of a Pivotal Trial.” Journal of Hematology &Amp; Oncology, 2023.

BibTeX Click to copy

@article{m2023a,
  title = {Treatment of adult ALL patients with third-generation CD19-directed CAR T cells: results of a pivotal trial},
  year = {2023},
  journal = {Journal of Hematology & Oncology},
  author = {Schubert, M. and Schmitt, A. and Hückelhoven-Krauss, Angela and Neuber, Brigitte and Kunz, Alexander and Waldhoff, Philipp and Vonficht, Dominik and Yousefian, S. and Jopp-Saile, L. and Wang, Lei and Korell, Felix and Keib, Anna and Michels, Birgit and Haas, Dominik and Sauer, T. and Derigs, P. and Kulozik, A. and Kunz, J. and Pavel, P. and Laier, Sascha and Wuchter, P. and Schmier, J. and Bug, G. and Lang, F. and Gökbuget, N. and Casper, J. and Görner, M. and Finke, J. and Neubauer, A. and Ringhoffer, M. and Wolleschak, D. and Brüggemann, M. and Haas, S. and Ho, A. D. and Müller-Tidow, C. and Dreger, P. and Schmitt, M.}
}

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 × 10^6 and 50 × 10^6 CARTs/m^2. 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.