Aggressive Lymphome (DLBCL, MCL) – was ist neu?

Was ist neu?

DLBCL. Biologie Der kürzlich publizierte „LymphGen-Algorithmus“ differenziert 7 genetische Subtypen, die sich in der Aktivierung onkogener Signalwege, im Genexpressionsmuster, im Tumormikromilieu, der Überlebenswahrscheinlichkeit und potenzieller zielgerichteter Therapien unterscheiden.

Erstlinientherapie Der Einsatz des neuen Antikörper-Wirkstoff-Konjugats Polatuzumab-Vedotin (6 Zyklen der Kombination aus Polatuzumab + R-CHP) waren der bisherigen Erstlinien-Standardtherapie mit R-CHOP hinsichtlich 2-Jahres-PFS überlegen. Subgruppenanalysen wiesen vor allem auf eine Wirksamkeit bei Patienten mit Hochrisikofaktoren hin.

Rezidivtherapie Seit Kurzem steht mit dem gegen den CD19 gerichteten Antikörper Tafasitamab in Kombination mit dem Immunmodulator Lenalidomid eine wirksame Rezidivtherapie für jene Patientengruppe zur Verfügung, die für eine Hochdosistherapie nicht geeignet ist. In 2 Phase-III-Studien wurde kürzlich bereits im 1. Rezidiv eine Überlegenheit von CAR-T-Zellen gegenüber dem bisherigen Standard der Hochdosistherapie, gefolgt von aPBSCT, gezeigt. Mit den bispezifischen, T-Zell-rekrutierenden CD3 / CD20-Antikörpern Mosunetuzumab, Epcoritamab und Glofitamab sind derzeit weitere vielversprechende immuntherapeutische Ansätze Gegenstand aktueller Phase I/II-Studien.

MCL. Biologie Trotz der weiteren Entschlüsselung des genetischen Hintergrunds des MCL ist weiterhin nur für TP53 eine klinische Relevanz nachgewiesen.

Erstlinientherapie In der Ära der zielgerichteten Therapiestrategien wird derzeit die Bedeutung des BTK-Inhibitors Ibrutinib für die Erstlinien- und Erhaltungstherapie des MCL evaluiert. Für ältere Patienten erwies sich kürzlich die Kombination des Proteasom-Inhibitors Bortezomib, Rituximab, Cyclophosphamid, Doxorubicin und Prednisolon (VR-CAP) der bisherigen Standardtherapie mit R-CHOP überlegen. Für ältere Patienten, die für intensivere Therapieregime nicht geeignet sind, führte die Erweiterung des klassischen Regimes Rituximab + Bendamustin um Ibrutinib zu einer deutlichen Verbesserung des PFS.

Rezidivtherapie Für das rezidivierte/refraktäre MCL wurden neben dem seit Jahren zugelassenen Ibrutinib kürzlich auch die beiden Next-Generation-BTK-Inhibitoren Acalabrutinib and Zanubrutinib zugelassen. Der bcl1-Inhibitor Venetoclax bietet für Hochrisikopatienten, die nach vorangegangener Therapie mit Ibrutinib ein Rezidiv erlitten, eine vielversprechende Behandlungsmöglichkeit. Bezüglich immuntherapeutischer Therapieansätze erfolgte kürzlich die Zulassung des CD19-CAR-T-Zell-Konstrukts Brexucabtagene autoleucel ab dem 2. Rezidiv.

Abstract

Our understanding of the molecular basis of the development and progression of malignant lymphoma has significantly improved over the last decades leading to the identification of genetic alterations with proven prognostic impact on the clinical course of the disease, such as TP53 mutations in MCL. This deepened molecular understanding sets the basis for the current rapid development regarding targeted and immuno-based therapies, offering individualized, risk-adapted treatment strategies in our near future with the potential to further improve patient care.

These new therapeutic alternatives are more and more being integrated in first-line treatments of DLBCL and MCL, among others, potentially replacing conventional chemotherapy-based treatment strategies. Yet, despite these promising new developments, clinical courses of patients with primary refractory disease or early relapses (< 12 months) are still characterized by only moderate responses and very limited overall survival even upon treatment with the available targeted treatment alternatives. For such high-risk patients, further optimized and individualized therapeutic strategies are highly warranted.

This article summarizes new findings regarding tumor biology and actual developments expanding the therapeutic landscape of DLBCL and MCL.

Schlüsselwörter

MCL - DLBCL - Biologie - Therapie

Key words

MCL - DLBCL - biology - therapy

Publication History

Article published online:
01 November 2022

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