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Was ist gesichert in der Therapie der akuten myeloischen Leukämie?

What is recommended in the treatment of acute myeloid leukemia?

  • Schwerpunkt: Was ist gesichert in der Therapie?
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Zusammenfassung

Die akute myeloische Leukämie (AML) entsteht durch eine maligne Transformation und Proliferation von myeloischen Vorläuferzellen, die zu einer Verdrängung der normalen Hämatopoese führt. Bei Erstdiagnose wird neben einer zytogenetischen Analyse auch die Mutationsdiagnostik von bei der AML häufiger mutierten Genen vorgenommen. Diese genetische Diagnostik ist wesentlich für die Risikostratifizierung und spätere Behandlung der Patienten. Für die intensiv behandelbaren Patienten wurden in den letzten Jahren drei neue Medikamente zugelassen: ein neuer Tyrosinkinaseinhibitor (Midostaurin) für Patienten mit einer FLT3-Mutation, eine besondere liposomale Zubereitung der Chemotherapie (CPX-351) für Formen der sekundären AML sowie ein CD33-Antikörper-Wirkstoff-Konjugat (Gemtuzumab-Ozogamicin) für die AML mit CD33-Expression. Die allogene Stammzelltransplantation bleibt die wesentliche Therapiekomponente für Patienten mit intermediärem und höherem Risiko sowie in der Rezidivsituation. Für ältere, nicht intensiv behandelbare Patienten ist der Einsatz von demethylierenden Substanzen die Therapie der Wahl. Ziel ist hier eine Lebensverlängerung bei akzeptabler Lebensqualität. In den letzten Jahren wurden auch für diese Patientengruppe neue vielversprechende Substanzen erfolgreich geprüft und in den USA bereits zugelassen. Dazu gehören der Bcl-2-Inhibitor Venetoclax, der in Deutschland bereits für die chronische lymphatische Leukämie zugelassen ist, sowie IDH1/IDH2-Inhibitoren für Patienten mit einer IDH1/IDH2-Mutation in ihren Leukämiezellen. Eine Sondergruppe der AML stellt die akute Promyelozytenleukämie dar, bei der eine Kombinationstherapie mit all-trans-Retinsäure und Arsentrioxid zu exzellenten Ergebnissen führt.

Abstract

Acute myeloid leukemia (AML) is characterized by a malignant transformation and proliferation of myeloid progenitor cells that cause a replacement of normal hematopoiesis. Diagnostic workup for AML includes cytogenetic analysis and mutational screening covering frequently mutated genes in AML. The genetic analysis is required for risk stratification and treatment decisions. Very recently, three novel drugs have been approved for patients who can be intensively treated: a tyrosine kinase inhibitor (midostaurin) for patients with FLT3 mutations, a liposomal formulation of chemotherapy (CPX) for patients with features of secondary AML, and a CD33 antibody–drug conjugate (gemtuzumab–ozogamicin) for AML with CD33 expression. Allogeneic stem cell transplantation remains an important treatment strategy for patients with intermediate- or high-risk AML and for patients with relapsed AML. For elderly patients who cannot undergo intensive treatment, demethylating agents are the treatment of choice. The aim is to prolong life expectancy with acceptable quality of life. In recent clinical trials, novel drugs have shown promising results in this patient population. Some of these drugs have already been approved in the US. Among these drugs are the Bcl‑2 inhibitor venetoclax, which is already approved in Germany for chronic lymphatic leukemia, as well as IDH1/IDH2 inhibitors (the latter for patients with IDH1/IDH2 mutated AML). Acute promyelocytic leukemia represents a special type of AML that should be treated with a combination of all-trans retinoic acid and arsenic trioxide leading to excellent outcome.

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Authors and Affiliations

  1. Klinik für Hämatologie, Hämostaseologie, Onkologie und Stammzelltransplantation, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, 30625, Hannover, Deutschland

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F. Thol weist auf folgende Beziehungen hin: Unterstützung klinischer Studien durch Astellas, Celgene, Novartis, Pfizer.

Für diesen Beitrag wurden von der Autorin keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.

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H. Haller, Hannover

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Thol, F. Was ist gesichert in der Therapie der akuten myeloischen Leukämie?. Internist 60, 1240–1250 (2019). https://doi.org/10.1007/s00108-019-00696-w

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