Maligne Lymphome – Quo vadis?

Die stetig fortschreitenden Entwicklungen in der Diagnostik und Therapie maligner Lymphome machen Hoffnung, stoßen aber auch immer wieder an Grenzen. Zielgerichtete und individualisierte Ansätze eröffnen immer mehr Möglichkeiten. Hier wollen wir einen Ausblick wagen und neue diagnostische und therapeutische Verfahren näher beleuchten, die derzeit noch nicht in der klinischen Routine angelangt sind, aber das Potenzial haben, in naher Zukunft die diagnostische und therapeutische Landschaft maligner Lymphome nachhaltig zu prägen.

Abstract

The diagnosis and treatment of malignant lymphoma is rapidly advancing, offering hope but also highlighting inherent limitations. Technological breakthroughs in sequencing technologies enable more precise subtyping and risk stratification. For example, in diffuse large B-cell lymphoma (DLBCL), exome sequencing revealed molecular subtypes. Understanding these subtypes sheds light on lymphomagenesis and prognosis, and may provide targets for tailored therapies. Additionally, tumor-derived cell-free DNA (ctDNA) detected in blood plasma allows for genotyping, risk stratification, and measurement of minimal residual disease (MRD). Current studies often examine drug effectiveness through “all-comer” approaches or in transcriptionally defined subtypes. Molecular agnostic studies increasingly focus on clinically defined high-risk patients (e.g., using the IPI) to better demonstrate the statistical significance of therapy effects. Improved patient selection can enhance the cost-effectiveness of modern, often expensive, therapies.

Kernaussagen

• Der technologische Fortschritt in den Sequenzier-Technologien erlaubt eine genauere Subtypisierung und Risikostratifizierung von malignen Lymphomen.

• Beim diffus großzelligen B-Zell-Lymphom (DLBCL) konnten durch Exom-Sequenzierung molekulare Subtypen identifiziert werden. Diese Subtypen erlauben nicht nur nähere Einblicke in die unterschiedliche Lymphoma-Genese und -Prognose, sondern sind möglicherweise auch durch gezielte Therapien angehbar.

• Vom Tumor abstammende zellfreie DNA (ctDNA) kann im Blutplasma detektiert werden und zur Genotypisierung, Risikostratifizierung und Messung minimaler Resterkrankung (MRD) herangezogen werden.

• In aktuellen Studienkonzepten wird die Wirksamkeit von Medikamenten meist noch in „All-Comer“-Studien oder in transkriptionell definierten Subtypen untersucht. Für molekularagnostische Studien werden zunehmend klinisch definierte Hochrisiko-Patienten selektioniert (z.B. mithilfe des IPI), um Therapieeffekte statistisch sichtbarer zu machen.

• Eine bessere Patientenauswahl kann die Wirtschaftlichkeit moderner, sehr teurer Therapien verbessern.

Schlüsselwörter

maligne Lymphome - Diagnostik - Therapie - molekularagnostisch - molekularinformiert - All comer-Studien

Keywords

malignant lymphomas - diagnosis - therapy - molecular agnostic - molecularly informed - all comer studies

Publication History

Article published online:
15 May 2024

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