Chronische lymphatische Leukämie – Standardtherapien und vielversprechende neue Behandlungsansätze

Die chronische lymphatische Leukämie (CLL) ist die häufigste Leukämie des Erwachsenen in der westlichen Welt und zeigt einen sehr variablen klinischen Verlauf. Die Heterogenität ist bedingt durch biologische Faktoren wie z. B. genomische Aberrationen und den Mutationsstatus der Immunglobulingene (IGHV). Die Therapieoptionen bei der chronisch lymphatischen Leukämie wurden über die vergangenen Jahre erheblich erweitert. Die Kombination aus Fludarabin, Cyclophosphamid und Rituximab (FCR) wurde als wirksamste Standardtherapie bei Patienten ohne relevante Komorbidität etabliert. Bendamustin kombiniert mit Rituximab (BR) wird gegenwärtig im Vergleich zu Rituximab untersucht und stellt eine Alternative dar. Chlorambucil ist weiterhin relevant bei älteren Patienten mit Komorbidität, wobei die Hinzunahme von Antikörpern eine Verbesserung bringt. Alemtuzumab ist eine Alternative für Hochrisikopatienten (refraktäre CLL, 17p Deletion, TP53 Mutation). Die allogene Stammzelltransplantation (allo-SCT) bietet die einzige kurative Option, allerdings bei relevanten Risiken. Innovative Therapieansätze fokussieren auf eine gezielte sowie individualisierte Behandlung und zeigen nach ersten Daten erhebliche Wirksamkeit bei hervorragender Verträglichkeit. Diese Übersichtsarbeit beschreibt die derzeitigen Standardtherapien und vielversprechende neue Behandlungsansätze.

Chronic lymphocytic leukemia (CLL) is the most common leukemia in the western world and is characterized by a highly variable clinical course. Among the biological features underlying this heterogeneity, genetic lesions and the mutational status of the immunoglobulin heavy chain variable genes (IGHV) are of importance. Therapeutic options in CLL have been considerably expanded during recent years. The combination of fludarabine, cyclophosphamide and rituximab (FCR) has become gold standard in the first-line treatment of physically fit patients. Bendamustine plus Rituximab (BR) is currently evaluated in comparison to FCR and constitutes an alternative to FCR. Chlorambucil is still of relevance for elderly patients with comorbidities and the addition of antibodies appears to enhance efficacy. Alemtuzumab is an alternative for high-risk patients (refractory CLL, 17p deletion, TP53 mutation). Allogeneic stem cell transplantation (allo-SCT) offers the only chance of cure but not without substantial mortality. Innovative approaches focus on individualized, targeted therapies. A number of novel agents are in clinical trials and show marked efficacy combined with good tolerability. This review provides an overview of the current therapeutic options and of promising novel approaches.

Key words

Chronic lymphocytic leukemia (CLL) - biology - therapy

• Literatur

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