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| Item Type: | Article |
|---|---|
| Title: | Treatment of adult ALL patients with third-generation CD19-directed CAR T cells: results of a pivotal trial |
| Creators Name: | Schubert, M.L., Schmitt, A., Hückelhoven-Krauss, A., Neuber, B., Kunz, A., Waldhoff, P., Vonficht, D., Yousefian, S., Jopp-Saile, L., Wang, L., Korell, F., Keib, A., Michels, B., Haas, D., Sauer, T., Derigs, P., Kulozik, A., Kunz, J., Pavel, P., Laier, S., Wuchter, P., Schmier, J., Bug, G., Lang, F., Gökbuget, N., Casper, J., Görner, M., Finke, J., Neubauer, A., Ringhoffer, M., Wolleschak, D., Brüggemann, M., Haas, S., Ho, A.D., Müller-Tidow, C., 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 × 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. |
| Keywords: | Cute Lymphoblastic Leukemia (ALL), Third-Generation Chimeric Antigen Receptor (CAR) T Cells, Investigator-Initiated Trial (IIT), CART-Associated Toxicities, Cytokine Release Syndrome (CRS), Cytopenia, Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), CD39 |
| Source: | Journal of Hematology & Oncology |
| ISSN: | 1756-8722 |
| Publisher: | BioMed Central |
| Volume: | 16 |
| Number: | 1 |
| Page Range: | 79 |
| Date: | 22 July 2023 |
| Official Publication: | https://doi.org/10.1186/s13045-023-01470-0 |
| PubMed: | View item in PubMed |
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