Neueste Erkenntnisse zum myelodysplastischen Syndrom

Zusammenfassung

Neuerungen – Klassifikation und Prognose Die WHO-2016-Klassifikation wurde durch die ICC und die Klassifikation der WHO 2022 abgelöst. Die beiden Klassifikationen weisen viele Ähnlichkeiten auf; den größten Unterschied stellt der Blastengrenzwert dar. Seit 2022 steht der IPSS-M, der molekulare Aberrationen berücksichtigt, zur Verfügung und verbessert im Vergleich zum IPSS-R die Prognosegenauigkeit für das progressionsfreie Überleben und das Gesamtüberleben. Somit soll eine optimierte therapeutische Entscheidungsfindung ermöglicht werden.

Neuerungen – Therapie 2020 wurde Luspatercept für transfusionsabhängige Patient*innen mit Ringsideroblasten ± einer SF3B1-Mutation zugelassen. Rezent konnte die Überlegenheit von Luspatercept in der ersten Linie gegenüber EPO gezeigt werden. Mit Imetelstat können wir in Zukunft ggf. eine neue Zweitlinientherapie für LR-MDS-Patient*innen nach Versagen von EPO anbieten. Für High-Risk-Patient*innen ist die Therapie mit Azacitidin weiterhin der Therapiestandard – die Ergebnisse der Phase-III-Studien der Kombinationstherapien müssen abgewartet werden.

Abstract

Myelodysplastic syndromes (MDS) represent a heterogeneous group of myeloid disorders characterized by peripheral blood cytopenias and increased risk of transformation to acute myeloid leukemia (AML).

Recent developments include the classification and the estimation of prognosis. In 2022 the former 2016 WHO classification was replaced by the ICC and WHO 2022 classification. Both classifications have included precursor lesions (CHIP and ICUS), both distinguish between three molecularly cytogenetically defined subgroups – del(5q), TP53, SF3B1 – and morphologically defined subgroups with differences in blast threshold (WHO: 20%; ICC: 10%) for the differentiation from AML. However, although prognostic factors influenced the classification-subgroups, it is important to distinguish the prognosis, which is crucial for optimal therapeutic decision making. Since 2022, the IPSS-M has been available for this purpose, which represents an expansion of the well-established IPSS-R. It could improve prognosis estimation by adding molecular data, recently this could have been confirmed in real world cohorts. The IPSS-M also represents an important extension with regard to prognosis estimation for patients with therapy-related MDS.

In 2020 Luspatercept has been approved for transfusion-dependent lower risk MDS patients harboring ring sideroblasts ± an SF3B1 mutation after failure of an erythropoiesis stimulating agent. The COMMANDS trial has just reported an interim analysis, where the superiority of luspatercept in the 1st line compared to erythropoietin could be demonstrated. In addition, data from the phase III trial with Imeltelstat give reason to hope that we will be able to offer a new second-line therapy to LR-MDS patients. For higher risk MDS patients azacitidine therapy remains the standard of care, results of phase III trials of combination therapies must be awaited.

Schlüsselwörter

myelodysplastisches Syndrom - ICC/WHO-Klassifikation 2022 - IPSS-M - Luspatercept

Keywords

myelodysplastic syndrome - ICC/WHO classification 2022 - IPSS-M - Luspatercept

Publication History

Article published online:
27 March 2024

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