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Third-generation anti-CD19 CAR T cells for relapsed/refractory chronic lymphocytic leukemia: a phase 1/2 study

Third-generation chimeric antigen receptor T cells (CARTs) for relapsed or refractory (r/r) chronic lymphocytic leukemia (CLL) may improve efficacy compared to second-generation CARTs due to their enhanced CAR design. We performed the first phase 1/2 investigator-initiated trial evaluating escalatin...

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Hauptverfasser: Derigs, Patrick (Verfasst von) , Schubert, Maria-Luisa (Verfasst von) , Dreger, Peter (Verfasst von) , Schmitt, Anita (Verfasst von) , Yousefian, Schayan (Verfasst von) , Haas, Simon (Verfasst von) , Röthemeier, Caroline (Verfasst von) , Neuber, Brigitte (Verfasst von) , Hückelhoven-Krauss, Angela (Verfasst von) , Brüggemann, Monika (Verfasst von) , Bernhard, Helga (Verfasst von) , Kobbe, Guido (Verfasst von) , Lindemann, Albrecht (Verfasst von) , Rummel, Mathias (Verfasst von) , Michels, Birgit (Verfasst von) , Korell, Felix (Verfasst von) , Ho, Anthony Dick (Verfasst von) , Müller-Tidow, Carsten (Verfasst von) , Schmitt, Michael (Verfasst von)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 27 August 2024
In: Leukemia
Year: 2024, Jahrgang: 38, Heft: 11, Pages: 2419-2428
ISSN:1476-5551
DOI:10.1038/s41375-024-02392-7
Online-Zugang:Verlag, kostenfrei, Volltext: https://doi.org/10.1038/s41375-024-02392-7
Verlag, kostenfrei, Volltext: https://www.nature.com/articles/s41375-024-02392-7
Volltext
Verfasserangaben:Patrick Derigs, Maria-Luisa Schubert, Peter Dreger, Anita Schmitt, Schayan Yousefian, Simon Haas, Caroline Röthemeier, Brigitte Neuber, Angela Hückelhoven-Krauss, Monika Brüggemann, Helga Bernhard, Guido Kobbe, Albrecht Lindemann, Mathias Rummel, Birgit Michels, Felix Korell, Anthony D. Ho, Carsten Müller-Tidow and Michael Schmitt
Beschreibung
Zusammenfassung:Third-generation chimeric antigen receptor T cells (CARTs) for relapsed or refractory (r/r) chronic lymphocytic leukemia (CLL) may improve efficacy compared to second-generation CARTs due to their enhanced CAR design. We performed the first phase 1/2 investigator-initiated trial evaluating escalating doses of third-generation CARTs (HD-CAR-1) targeting CD19 in patients with r/r CLL and B-cell lymphoma. CLL eligibility criteria were failure to two therapy lines including at least one pathway inhibitor and/or allogeneic hematopoietic cell transplantation. Nine heavily pretreated patients received HD-CAR-1 at dose levels ranging from 1 × 106 to 200 × 106 CART/m2. In-house HD-CAR-1 manufacturing was successful for all patients. While neurotoxicity was absent, one case of grade 3 cytokine release syndrome was observed. By day 90, six patients (67%) attained a CR, five of these (83%) with undetectable MRD. With a median follow-up of 27 months, 2-year PFS and OS were 30% and 69%, respectively. HD-CAR-1 products of responders contained significantly more CD4 + T cells compared to non-responders. In non-responders, a strong enrichment of effector memory-like CD8 + T cells with high expression of CD39 and/or CD197 was observed. HD-CAR-1 demonstrated encouraging efficacy and exceptionally low treatment-specific toxicity, presenting new treatment options for patients with r/r CLL. Trial registration: #NCT03676504.
Beschreibung:Gesehen am 05.09.2025
Beschreibung:Online Resource
ISSN:1476-5551
DOI:10.1038/s41375-024-02392-7

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