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CAR-T-Zellen zur Behandlung von malignen B-Zell-Lymphomen

Ein neues Therapieprinzip

CAR T-cell therapy for malignant B-cell lymphoma

A new treatment paradigm

  • Schwerpunkt: Zelluläre Immuntherapien in der Onkologie: CAR-T-Zellen
  • Published:
Der Internist Aims and scope Submit manuscript

Zusammenfassung

Nachdem 2011 erstmalig die Wirksamkeit von gegen CD19 gerichteten CAR-T-Zellen (CAR chimärer Antigenrezeptor) bei einem Patienten mit rezidivierter chronischer lymphatischer Leukämie (CLL) gezeigt werden konnte, wurden die Zulassungsstudien für diese innovative Therapie zunächst bei der mehrfach rezidivierten oder refraktären (r/r) akuten B‑Zell-Leukämie im Kindes- und jungen Erwachsenenalter und beim aggressiven B‑Zell-Lymphom erwachsener Patienten durchgeführt. Die Studien zeigten Wirksamkeit sogar bei chemotherapierefraktären Krankheitsverläufen, sodass mit dem Produkt Tisagenlecleucel (Kymriah®, Novartis) die ersten autologen und gentechnisch modifizierten T‑Zellen bereits 2018 für die Behandlung der r/r akuten lymphatischen B‑Zell-Leukämie (B-ALL) in den USA zugelassen wurden. Die Zulassung zur Behandlung r/r aggressiver B‑Zell-Lymphome erfolgte kurz darauf für Tisagenlecleucel und Axicabtagen Ciloleucel (Yescarta, Kite/Gilead). Die vorliegende Übersicht konzentriert sich auf die Behandlung des aggressiven B‑Zell-Lymphoms und anderer CD19-positiver B‑Zell-Lymphome. Dafür werden die Studienergebnisse klinisch geprüfter CAR-T-Zellen zusammengefasst, mögliche Resistenzmechanismen erörtert und ein Ausblick auf laufende Studien mit neuen Zielantigenen für die Behandlung von B‑Zell-Lymphomen gegeben.

Abstract

Following the first demonstration of efficacy of anti-CD19-directed chimeric antigen receptor (CAR) T cells in a patient with relapsed chronic lymphocytic leukemia (CLL) in 2011, pivotal studies for this innovative therapy were initially conducted in multiple relapsed or refractory (r/r) childhood and young adult acute B‑cell leukemia and in aggressive adult B‑cell lymphoma. The studies demonstrated efficacy even in chemotherapy-refractory disease, resulting in the first approval of autologous and genetically engineered T cells for the treatment of r/r B‑cell acute lymphoblastic leukemia (B-ALL) in the US for the product tisagenlecleucel (Kymriah®, Novartis) back in 2018. Approval for the treatment of r/r aggressive B‑cell lymphoma followed shortly thereafter for tisagenlecleucel and axicabtagene ciloleucel (Yescarta, Kite/Gilead). This review focuses on the treatment of aggressive B‑cell lymphoma and other CD19 positive B‑cell lymphomas by summarizing the study results of clinically tested CAR T cells, discussing possible resistance mechanisms, and providing an outlook on ongoing studies with new target antigens for the treatment of B‑cell lymphomas.

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  1. Uniklinik Köln, Medizinische Klinik 1, 50937, Köln, Deutschland

    H. Balke-Want &  P. Borchmann

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P. Borchmann ist Consultant für Takeda, BMS, Roche, Amgen, Novartis, Celgene, Miltenyi Biotec und Gilead. Er erhält Forschungsunterstützung und Hornorare von Novartis, Takeda und MSD sowie Honorare von BMS, Roche, Celgene, Miltenyi Biotec, Gilead und AbbVie. H. Balke-Want gibt an, dass kein Interessenkonflikt besteht.

Für diesen Beitrag wurden von den Autoren keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.

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Balke-Want, H., Borchmann, P. CAR-T-Zellen zur Behandlung von malignen B-Zell-Lymphomen. Internist 62, 589–596 (2021). https://doi.org/10.1007/s00108-021-01056-3

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