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. 2025 Jul;65(7):490-499.
doi: 10.1007/s00117-025-01472-8. Epub 2025 Jun 13.

[Modern systemic treatment-bispecific antibodies and CAR-T cell therapy : Clinical management, mechanisms of action, outcomes]

[Article in German]
Henriette Huber  1   2 , Elke Leupolt  1 , Lukas Kündgen  1 , Martin Bentz  3
Affiliations

[Modern systemic treatment-bispecific antibodies and CAR-T cell therapy : Clinical management, mechanisms of action, outcomes]

[Article in German]
Henriette Huber et al. Radiologie (Heidelb). 2025 Jul.

Abstract
in English, German

Background: Despite chemoimmunotherapy and autologous stem cell transplants, 30-40% of all patients with aggressive B‑cell non-Hodgkin lymphoma relapse.

Objective: The use of targeted therapies is necessary to optimize the survival of these patients.

Results: Chimeric antigen receptor (CAR) T‑cell therapies directed against CD19 are increasingly changing the therapeutic landscape for patients with diffuse large B‑cell lymphoma (DLBCL) and other B‑cell non-Hodgkin lymphomas. Follow-up data show that 30-40% of patients with relapsed or refractory aggressive lymphomas remain disease-free and can be cured in the long term after CAR-T cell therapy. Increasingly improved management of side effects, e.g., cytokine release syndrome (CRS) and neurotoxicity (immune effector cell-associated neurotoxicity syndrome, ICANS), by trained teams improves treatment safety. Bispecific antibodies are also targeted therapies that bind and activate CD3 effector T‑cells and assemble them into B‑cell antigens in the sense of an immunological synapse, resulting in cell-dependent cytotoxicity. Some of these drugs are also approved for aggressive and some for indolent B‑cell non-Hodgkin lymphoma; they are available off the shelf and can also be used in particular for older and less fit patients.

Conclusion: Both treatment options have significantly improved the prognosis of patients with lymphoma and generally have lower toxicities.

Zusammenfassung: HINTERGRUND: Trotz klassischer Chemoimmuntherapie und autologer Stammzelltransplantationen kommt es bei 30–40 % aller Patienten mit aggressiven Lymphomen zu einem Rezidiv.

Fragestellung: Zur Optimierung des Überlebens dieser Patienten ist der Einsatz von zielgerichteten Therapien notwendig.

Ergebnisse: Chimäre, gegen CD19 gerichtete Antigenrezeptor-T-Zell-Therapien verändern zunehmend die therapeutische Landschaft für Patienten mit diffusem großzelligem B‑Zell-Lymphom (DLBCL) und anderen B‑Zell-Non-Hodgkin-Lymphomen. Nachbeobachtungsdaten zeigen, dass 30–40 % der Patienten mit rezidivierten oder refraktären aggressiven Lymphomen nach einer chimäre Antigenrezeptor(CAR)-T-Zell-Therapie langfristig krankheitsfrei bleiben und geheilt werden können. Ein zunehmend verbessertes Nebenwirkungsmanagement von Zytokinfreisetzungssyndrom („cytokine release syndrome“, CRS) und Neurotoxizität („immune effector cell-associated neurotoxicity syndrome“, ICANS) im geschulten Team verbessert die Einsatzfähigkeit. Bispezifische Antikörper sind ebenfalls zielgerichtete Therapien, die CD3-Effektor-T-Zellen binden, aktivieren und sie mit B‑Zell-Antigenen im Sinne einer immunologischen Synapse zusammenführen, was zu einer zellabhängigen Zytotoxizität führt. Auch von diesen Substanzen sind einige für aggressive und einige für indolente B‑Zell-Non-Hodgkin Lymphome zugelassen, „off the shelf“ verfügbar und insbesondere auch für ältere und weniger fitte Patienten einsetzbar.

Schlussfolgerung: Beide Therapieoptionen haben prognostisch die Therapielandschaft für Patienten mit Lymphomen deutlich verbessert bei im Allgemeinen geringerer Toxizität.

Keywords: B‑cell non-Hodgkin lymphoma; Cytokine release syndrome; Diffuse large B‑cell lymphoma; Neurotoxicity; Recurrence.

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Conflict of interest statement

Einhaltung ethischer Richtlinien. Interessenkonflikt: H. Huber: Vortragshonorare von AbbVie, Janssen-Cilag, BeiGene, Lilly; Advisory Boards: Janssen-Cilag, BeiGene. M. Bentz: Vortragshonorare: Roche, Janssen-Cilag, AbbVie, Sanofi-Aventis; Advisory Boards: AbbVie, Gilead, Janssen-Cilag. E. Leupolt und L. Kündgen geben an, dass kein Interessenkonflikt besteht. Für diesen Beitrag wurden von den Autor/-innen keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.

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