Chronisch myeloische Leukämie

Was ist neu?

Therapieentscheidung Neben der Wirksamkeit spielen individuelle Therapieziele, Komorbiditäten, Komedikationen und auch Compliance-Themen eine zunehmende Rolle bei der Auswahl des individuell zu präferierenden Tyrosinkinase-Inhibitors (TKI).

Nebenwirkungen Hier gilt es, die sog. Klasseneffekte (ein Effekt, der unter allen TKIs bei einer bestimmten Klasse von TKIs auftreten kann) von den substanzspezifischen Nebenwirkungen der einzelnen TKIs zu unterscheiden.

Was tun bei Nebenwirkungen und Unverträglichkeit? In Studien konnte gezeigt werden, dass durch Anpassung der Dosis des TKIs (ggf. auch mit zeitlich begrenzter Therapiepause) und/oder Änderung der Begleitmedikation eine Verbesserung der Therapietreue (Adhärenz) in den meisten Fällen erreicht werden konnte.

Wie können TKI-Nebenwirkungen vermieden werden? Zur Evaluation der Belastungen und Einschränkungen ist eine gute Arzt-Patienten-Interaktion entscheidend. Hiermit wird das Therapieziel einer guten Wirksamkeit und Adhärenz am ehesten erreicht.

Abstract

The introduction of orally available tyrosine kinase inhibitors (TKI) into the treatment of chronic myeloid leukemia (CML) 25 years ago has substantially improved the clinical outcome of affected patients and resulted in a near-normal life expectancy in chronic phase (CP). Despite of a significant fraction of currently about one third of newly diagnosed CP patients eventually reaching treatment-free remission, the majority of patients still remain on life-long treatment with TKIs. Therefore, a profound knowledge of TKI-related side effects including an increased sensitivity for organ systems predominantly involved, grading, kinetics, duration and reversibility, class-effects versus compound-relatedness as well as a better understanding of how particularly long-lasting, chronic, sometimes formally low-grade toxicities can actually significantly impair patient’s self-assessed quality of life is of utmost importance for an adequate patient/doctor relationship. Given that nowadays, severity and degree of preexisting comorbidities might predict long-term survival of individual patients more significantly than the underlying CML itself, it becomes most important to properly and thoroughly select the TKI of choice on this basis as well as on the individually required co-medications. Given the variety of 2nd, 3rd and now allosteric TKIs available for the molecular targeting of the disease-driving BCR-ABL oncogene in addition to the “class-defining” Imatinib, personalization of CML therapy should now be further extended towards a better appreciation of comorbidities and co-medications before selection of an individual’s TKI treatment complemented by a long-term oriented, patient-centered management and prevention of (sometimes irreversible) TKI side effects.

Schlüsselwörter

Leukämie - CML - Cytochrom P450 (CYP450) - Tyrosinkinaseinhibitor - TKI-Wechselwirkungen

Keywords

Leukemia - cytochrome P450 (CYP450) - tyrosine kinase inhibitor - TKI interactions - CML

Publication History

Article published online:
31 May 2023

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