Checkpoint-Inhibitoren bei Hodgkin-Lymphom

Checkpoint inhibitors in Hodgkin lymphoma

Zusammenfassung

Hintergrund

Der immunmodulatorische Ansatz der Checkpointblockade trägt der Rolle des immunsuppressiv wirkenden Mikromilieus („microenvironment“) beim klassischen Hodgkin-Lymphom (cHL) und dabei insbesondere der Interaktion der Hodgkin-Zellen und Makrophagen mit umgebenden T‑ und natürlichen Killerzellen über „programmed cell death 1 ligand 1“ (PD-L1) und „programmed cell death 1“ (PD-1) Rechnung.

Ziel der Arbeit

Erarbeitung der Rolle und des Potenzials der Checkpointblockade beim cHL vor dem Hintergrund der Resultate der standardmäßigen Chemo- und Strahlentherapiekonzepte.

Methoden

Analyse der präklinischen und klinischen Daten (Phase-I- und Phase-II-Studien) der Checkpointblockade beim cHL.

Ergebnisse und Diskussion

Bei 60–70 % der Patienten mit chemotherapierefraktärem cHL kann durch die PD-1-Blockade ein Ansprechen erzielt werden; ein persistierendes Ansprechen ist selten, die Überlebensdaten sind dennoch exzellent. Daher stellt die Anwendung von Anti-PD-1-Antikörpern einen wichtigen Bestandteil der Rezidivtherapie des cHL entsprechend den Zulassungsempfehlungen dar. Die Daten in der Erstlinientherapie sind noch vorläufig; erste Phase-II-Studien, in denen der Anti-PD-1-Antikörper Nivolumab in Kombination mit Doxorubicin (=Adriamycin), Vinblastin und Dacarbazin (AVD) in den intermediären bzw. fortgeschrittenen Stadien angewandt wurde, ergaben Ansprechraten von 90 % bzw. 67 % und deuten darauf hin, dass durch Implementierung des immunmodulatorischen Ansatzes der PD-1-Blockade die erforderliche Chemotherapieintensität signifikant gesenkt werden kann. Dies würde einen Paradigmenwechsel in der Therapie des cHL bedeuten.

Abstract

Background

Checkpoint blockade contributes to the immunosuppressive microenvironment in classical Hodgkin lymphoma (cHL) and in particular the interaction of Hodgkin cells and macrophages with T‑cells and natural killer cells via programmed cell death 1 (PD-1) and programmed cell death 1 ligand 1 (PD-L1).

Objectives

The aim of this article is the evaluation the role and potential of checkpoint blockade in cHL as compared with the results of standard chemo- and radiotherapy.

Methods

We analyzed preclinical and clinical data from phase I and phase II studies with checkpoint blockade in cHL.

Results and discussion

In 60–70% of patients with chemotherapy-refractory cHL, PD‑1 blockade results in responses. Overall survival is excellent and a small number of patients achieve persistent response. Thus, the use of anti-PD‑1 monoclonal antibodies has become an important treatment approach in relapsed cHL in line with the label. The results of first-line therapy are still preliminary; initial phase II studies using nivolumab in combination with doxorubicin (=adriamycin), vinblastin and dacarbazin (AVD) in early unfavorable or advanced stages showed response rates of up to 90%. Thus, implementing immunomodulatory approaches using PD 1‑blockade have resulted in a significant reduction of chemotherapy. This might represent a paradigm shift in the therapy of cHL.

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Authors

Corresponding author

Correspondence to Prof. Dr. A. Engert.

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Interessenkonflikt

S. Sasse und J. Momotow geben an, dass kein Interessenkonflikt besteht. A. Engert: Beratungs- und Gutachtertätigkeit: Takeda/Millennium, BMS, MSD, Affimed.

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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M. Hallek, Köln

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Cite this article

Sasse, S., Momotow, J. & Engert, A. Checkpoint-Inhibitoren bei Hodgkin-Lymphom. Internist 61, 660–668 (2020). https://doi.org/10.1007/s00108-020-00811-2

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Schlüsselwörter

  • Chemotherapierefraktäres Hodgkin-Lymphom
  • Immunmodulation
  • Immunsuppressives Tumormikromilieu
  • „Programmed cell death 1“ (PD-1)
  • Nivolumab

Keywords

  • Hodgkin disease, chemotherapy-refractory
  • Immunomodulation
  • Tumor microenvironment, immunosuppressive
  • Programmed cell death 1 (PD-1)
  • Nivolumab