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Periphere T‑Zell-Lymphome

Primär- und Rezidivtherapie

Peripheral T‑cell lymphomas

Primary and relapsetreatment

  • Leitthema
  • Published:
Der Onkologe Aims and scope

Zusammenfassung

Hintergrund

Als periphere T‑Zell-Lymphome (PTCL) wird eine heterogene Gruppe klinisch aggressiver Erkrankungen mit dem Phänotyp reifer T‑Zellen und schlechter Prognose zusammengefasst. Neue Therapien werden intensiv untersucht und können die Behandlung für einige Subtypen schon in naher Zukunft verbessern.

Fragestellung

Der aktuelle Wissenstand zu PTCL mit Fokus auf moderne Therapiestandards und neue therapeutische Optionen wird dargestellt.

Methode

Basierend auf einer selektiven Literaturreche werden Grundlagenarbeiten und Leitlinien diskutiert.

Ergebnisse

Aktueller Konsens für die Erstlinientherapie von PTCL sind anthrazyklinhaltige Kombinationschemotherapien, abhängig vom Subtyp und Erkrankungsstadium gefolgt von autologer Stammzelltransplantation. Darunter ist für etwa 50 % der Patienten eine langfristige Erkrankungsfreiheit zu erwarten; bei 30 % der PTCL-Patienten sind die Lymphome primär refraktär. Im Rezidiv ist die Prognose bei alleinigem Einsatz von Zytostatika sehr ungünstig. Für geeignete Patienten stellt die allogene Stammzelltransplantation ein Verfahren mit der Chance auf eine langfristige Erkrankungskontrolle dar. Für Patienten mit anaplastischen großzelligen T‑Zell-Lymphomen steht mit dem gegen CD30 gerichteten Antikörper-Chemotherapie-Konjugat Brentuximab Vedotin im Rezidiv eine effektive Therapie zur Verfügung. Auch in der Erstlinientherapie wurde für Brentuximab Vedotin in Kombination mit Chemotherapie ein erhöhter Nutzen bei CD30-positiven PTCL nachgewiesen. Das zunehmend vertiefte Verständnis der Biologie und Pathogenese von PTCL führt zur Testung weiterer zielgerichteter Therapien als Monotherapie und in Kombinationen. So wurde in den letzten Jahren die Inhibition von Histondeacetylase (HDAC) auf Ebene der epigenetischen Regulation geprüft. Unter den innovativen Therapieprinzipien wurden vor allem mit der Inhibition der Phosphoinositid-3-Kinasen (PI3K) auf Ebene der Signaltransduktion ermutigende Ansprechraten für Patienten mit rezidivierter oder refraktärer Erkrankung erreicht.

Schlussfolgerung

Die aktuelle Behandlung der PTCL basiert auf Chemotherapie- und Transplantationskonzepten. Aktuell werden für viele PTCL-Subtypen potenziell effektivere Therapien entwickelt.

Abstract

Background

Peripheral T‑cell lymphomas (PTCL) comprise a heterogeneous group of lymphomas with a mature T‑cell phenotype, mostly presenting as aggressive disease with a poor prognosis. Innovative therapies are currently under investigation and may change the treatment of some PCTL subtypes in the near future.

Objectives

The aim of this article is to present the management of PTCL with a focus on current treatment standards and new therapy options.

Methods

A selective literature search was conducted and guidelines are discussed.

Results

Anthracycline-based chemotherapy like CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) represents the preferred front-line treatment. Depending on the PTCL entity and the extent of disease, autologous stem cell transplantation is offered to eligible patients allowing long-term remission in about 50% of cases. Approximately 30% of patients face primary refractory disease. The prognosis for patients with relapsed and refractory disease is poor with chemotherapy-based salvage, but for eligible patients allogeneic stem cell transplantation represents an option for long-term disease control. For patients with relapsed anaplastic large cell lymphoma, the anti-CD30 antibody drug conjugate brentuximab-vedotin is an effective therapeutic option, and brentuximab-vedotin in combination with chemotherapy has also shown benefit in the first-line setting compared to conventional chemotherapy in patients with CD30-positive PTCL. Based on an improved understanding of pathophysiological mechanisms, new targeted drugs and drug combinations are currently under investigation, e.g. inhibition of histondeacetylase (HDAC) activity at the level of epigenetic regulation, as well as the inhibition of phosphoinositide 3‑kinase (PI3K) activity at the level of signal transduction, yielding encouraging response rates for patients with relapsed or refractory disease.

Conclusion

The current management of PTCL is based on chemotherapy and stem cell transplantation concepts. New therapies that are more effective are currently under development for many PTCL entities.

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Authors and Affiliations

  1. Universitätsmedizin Göttingen, Göttingen, Deutschland

    G. Wulf

  2. Medizinische Fakultät der Martin-Luther-Universität Halle-Wittenberg, Klinik und Poliklinik für Innere Medizin IV – Hämatologie und Onkologie, Universitätsklinikum Halle (Saale), Ernst-Grube-Str. 40, 06120, Halle (Saale), Deutschland

    T. Weber

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Correspondence to T. Weber.

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Interessenkonflikt

G. Wulf und T. Weber geben 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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Wulf, G., Weber, T. Periphere T‑Zell-Lymphome. Onkologe 25, 892–898 (2019). https://doi.org/10.1007/s00761-019-0636-8

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  • DOI: https://doi.org/10.1007/s00761-019-0636-8

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