Journal Article

DKFZ-2023-01426

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Treatment of adult ALL patients with third-generation CD19-directed CAR T cells: results of a pivotal trial.

Schubert, M.-L. ; Schmitt, A. ; Hückelhoven-Krauss, A. ; Neuber, B. ; Kunz, A. ; Waldhoff, P. ; Vonficht, D.DKFZ* ; Yousefian, S. ; Jopp-Saile, L.DKFZ* ; 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.DKFZ* ; Ho, A. D.DKFZ* ; Müller-Tidow, C.DKFZ* ; Dreger, P.DKFZ* ; Schmitt, M.DKFZ*

2023
Biomed Central London

This record in other databases:  

Please use a persistent id in citations: doi:10.1186/s13045-023-01470-0

Abstract: 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).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.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.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.gov as NCT03676504.

Keyword(s): Humans (MeSH) ; Adult (MeSH) ; Neurotoxicity Syndromes (MeSH) ; Leukapheresis (MeSH) ; Adaptor Proteins, Signal Transducing (MeSH) ; Antigens, CD19: therapeutic use (MeSH) ; Acute lymphoblastic leukemia (ALL) ; CART-associated toxicities ; CD39 ; Cytokine release syndrome (CRS) ; Cytopenia ; Immune effector cell-associated neurotoxicity syndrome (ICANS) ; Investigator-initiated trial (IIT) ; Third-generation chimeric antigen receptor (CAR) T cells ; cell-associated neurotoxicity ; Adaptor Proteins, Signal Transducing ; Antigens, CD19

Note: DKFZ-ZMBH Alliance

---

Contributing Institute(s):

1. A010 Stammzellen und Krebs (A010)
2. DKTK HD zentral (HD01)

Research Program(s):

1. 311 - Zellbiologie und Tumorbiologie (POF4-311) (POF4-311)

Appears in the scientific report 2023

---

Database coverage:
; ; Article Processing Charges ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; DOAJ Seal ; Ebsco Academic Search ; Essential Science Indicators ; Fees ; IF >= 25 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

---