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Dtsch Med Wochenschr 2024; 149(11): 630-637
DOI: 10.1055/a-2160-5320
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T-Zell-rekrutierende Immuntherapien des B-Zell-Lymphoms – bald in allen Therapielinien?

T-cell recruiting immunotherapies in B-cell lymphoma – the future backbone for all therapy lines?
Veit Bücklein
,
Bastian von Tresckow
,
Marion Subklewe
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Mit Rituximab hat die Immuntherapie bereits vor Jahrzehnten Einzug in die Routinebehandlung von B-Zell-Lymphomen gehalten. Die Zulassung neuer bispezifischer T-Zell-rekrutierender Antikörper und der adoptiven Immuntherapie mit CAR-T-Zellen bringt tiefgreifende Änderungen der Therapiealgorithmen bei aggressiven und indolenten Lymphomen mit sich. Im Folgenden werden die wichtigsten aktuell zugelassenen T-Zell-rekrutierenden Behandlungsstrategien vorgestellt.

Abstract

The introduction of immunologically targeted therapies has represented a significant advancement in the treatment of B-cell lymphomas, particularly aggressive B-cell lymphoma. CD19 CAR-T cells such as Axicabtagen-Ciloleucel (Axi-cel) and Lisocabtagen Maraleucel (Liso-cel) have been approved since 2022 and 2023, respectively, for second-line therapy of Diffuse Large B-Cell Lymphomas (DLBCL), when there is primary refractory disease or relapse within 12 months after the end of first-line therapy. These therapies result in a significant improvement in progression-free survival compared to the previous standard therapy (salvage chemotherapy followed by high-dose chemotherapy and autologous stem cell transplantation). Especially in elderly patients or patients with underlying medical conditions, CAR-T cell therapies like Axi-cel and Liso-cel demonstrate acceptable tolerability and high efficacy.

Furthermore, bispecific T-cell-engaging antibodies (“bispecifics”) such as Glofitamab, Epcoritamab, and Mosunetuzumab also represent promising treatment options for patients with relapsed disease after failure of second- or later line therapy and show efficacy even in a subset of patients relapsing after CD19 CAR-T cells. However, randomized study results for these substances are not yet available. They are expected to be used in earlier lines of therapy in the future, especially in combination with standard chemotherapy regimens. Common side effects of bispecific antibody therapies are cytokine release syndrome (CRS) and immune-mediated cytopenias, whereas immune-cell associated neurotoxicity syndrome (ICANS) is relatively rare compared to CD19 CAR T cells. In summary, bispecifics represent a novel, highly effective immunotherapy for the treatment of lymphomas with a very favourable toxicity profile.

Kernaussagen

  • CAR-T-Zellen und bispezifische Antikörperkonstrukte sind T-Zell-rekrutierende Behandlungskonzepte: Sie induzieren mittels patienteneigenen T-Zellen eine T-Zell-Antwort gegen B-Zell-Lymphomzellen.

  • Die in der Behandlung von B-Zell-Lymphomen zur Anwendung kommenden CAR-T-Zell-Präparate sind alle gegen CD19 als B-Zell-Antigen gerichtet, unterscheiden sind aufgrund verschiedener kostimulatorischer Domänen aber im Nebenwirkungsprofil (und möglicherweise auch in ihrer Anti-Lymphom-Wirksamkeit). Zulassungen existieren für DLBCLs (nach Versagen der Erstlinientherapie), für Mantelzelllymphome und follikuläre Lymphome (nach Versagen der Zweitlinientherapie).

  • Bispezifische Antikörper in der Behandlung von B-Zell-Lymphomen erkennen CD20 auf B-Zellen. Zulassungen existieren für DLBCLs und für follikuläre Lymphome (jeweils nach Versagen der Zweitlinientherapie).

  • CAR-T-Zellen und Bispecifics sind mit einer Reihe spezifischer Nebenwirkungen assoziiert (CRS, ICANS und a.e. immunvermittelten Zytopenien), deren Management spezifische Expertise erfordert. Von besonderer Bedeutung auch im längerfristigen Verlauf nach Therapie sind Infektionen, die ein schnelles ärztliches Eingreifen erfordern.

Schlüsselwörter

Immuntherapie - B-Zell-Lymphom - CAR-T-Zellen - bispezifische Antikörper - ADC

Keywords

immunotherapy - B-cell lymphoma - CAR T cells - bispecific antibodies - ADC


Publication History

Article published online:
15 May 2024

© 2024. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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