Erstlinienbehandlung älterer Patienten mit CLL: Ein neuer Ansatz ohne Chemotherapie

Für die Therapie der chronischen lymphatischen Leukämie (CLL) stehen inzwischen zahlreiche, zielgerichtete Therapien zur Verfügung, die sowohl in der Erst- als auch in der Zweitlinientherapie eine überlegene Wirksamkeit und eine längere Ansprechdauer im Vergleich zur Chemoimmuntherapie zeigen. Insbesondere ältere und gebrechliche Patienten profitieren von der besseren Verträglichkeit dieser Medikamente, die individuell unter Berücksichtigung von Begleiterkrankungen und Komedikation eingesetzt werden.

Abstract

Nowadays, a wide range of targeted therapies are available for the treatment of chronic lymphocytic leukemia, offering superior efficacy and a longer-lasting responses compared to chemoimmunotherapy in both first- and second-line settings. Owing to the favorable tolerability of novel targeted agents, genetic factors have superseded age and fitness as key determinants in the selection of first-line therapy. Currently, high-risk genetic features include del(17p13) or TP53 mutations, complex karyotype (≥3 chromosomal aberrations), and unmutated IGHV status. Initial risk stratification focuses on detecting del(17p13)/TP53 mutations and assessing karyotype. This new strategy, along with the improved tolerability of these agents, offers particular benefit to older and frail patients, with dosing tailored to comorbidities and concomitant therapies.

Given the heterogeneity in older patients' health status, geriatric assessments (e.g., CIRS, FRAIL score) are additional key for individualized therapy decisions and adverse events influence therapy choice (e.g. cardiovascular risk with BTK inhibitors. Beyond clinical factors, patient preferences—such as opting for continuous (e.g., BTK inhibitor monotherapy) versus time-limited therapy (e.g., venetoclax plus obinutuzumab or ibrutinib plus venetoclax)—and treatment tolerability are decisive.

Kernaussagen

• In der Erstlinienbehandlung jüngerer und älterer Patienten mit chronischer lymphatischer Leukämie (CLL) haben zielgerichtete Therapien (z.B. BTK- und BCL2-Inhibitoren) die klassische Chemoimmuntherapie fast vollständig ersetzt, da sie wirksamer und verträglicher sind.

• Anstelle von Alter und Fitness sind genetische Marker (z.B. TP53-Mutation/Deletion 17p, IGHV-Mutationsstatus, komplexer Karyotyp) entscheidend für die Wahl der optimalen Erstlinientherapie.

• Ältere Patienten unterscheiden sich stark in ihrer Gesundheit; daher sind geriatrische Assessments (z.B. CIRS- oder FRAIL-Score) wichtig für eine personalisierte Therapieentscheidung.

• BTK-Inhibitoren (Ibrutinib, Acalabrutinib, Zanubrutinib) sind mit kardiovaskulären Risiken (z.B. Vorhofflimmern, Hypertonie) verbunden, während BCL2-Inhibitoren (Venetoclax) das Risiko eines Tumorlysesyndroms erhöhen und bei höhergradiger Niereninsuffizienz kontraindiziert sind.

• Neben medizinischen Faktoren sind individuelle Wünsche entscheidend, etwa die Wahl zwischen einer Dauertherapie (z.B. BTK-Inhibitoren als Monotherapie) und einer zeitlich begrenzten Therapie (z.B. Venetoclax + Obinutuzumab oder Ibrutinib + Venetoclax) sowie die Verträglichkeit der Medikamenteneinnahme.

Schlüsselwörter

CLL Erstlinientherapie - zielgerichtete Therapie - älteren Patienten - BTK-Inhibitoren CLL - Venetoclax Obinutuzumab - ohne Chemotherapie

Keywords

first-line therapy - targeted therapy - elderly patients - BTK inhibitors CLL - Venetoclax Obinutuzumab - without chemotherapy

Publication History

Article published online:
10 October 2025

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