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Klinik und Therapie des multiplen Myeloms

Clincal features and treatment of multiple myeloma

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Zusammenfassung

Diagnostik und Therapie des multiplen Myeloms (MM) entwickeln sich kontinuierlich weiter. Dieser Beitrag fasst den aktuellen Stand der Diagnostik und Therapie zusammen.

Die Prognoseabschätzung und Risikostratifizierung beim MM erfolgen sowohl an Hand klinischer (International Staging System, ISS), molekularbiologischer Parameter sowie unter Einbeziehung des biologischen Zustands (Alter, Komorbiditäten) der Myelompatienten. Insbesondere das ISS und zytogenetische Merkmale (Hochrisikoaberrationen: Deletion 17p, Translokation (4;14) und Zugewinn 1q21 > 2 Kopien) spielen zur Prognoseabschätzung eine entscheidende Rolle. In der Erstlinientherapie ist die Induktionstherapie mit neuen Substanzen, vornehmlich Bortezomib, und anschließender Hochdosistherapie mit Melphalan und autologer Stammzelltransplantation der Standard für junge Patienten (bis 70 Jahre). Für nicht transplantationsfähige Patienten ist die Thalidomid- oder Bortezomib-basierte konventionelle Primärtherapie Mittel der Wahl. Es wurde nachgewiesen, dass die Kombination aus Bortezomib/Melphalan/Prednison (VMP) das Gesamtüberleben gegenüber alleinigem Melphalan/Prednison (MP) signifikant verlängert (VMP vs. MP, 56,4 vs. 43,1 Monate; p = < 0,01). Aktuelle Studien untersuchen eine Lenalidomid-basierte, alkylanzienfreie Primärtherapie für nicht transplantationsfähige Patienten. Erste Ergebnisse deuten auf ein günstigeres Nebenwirkungsprofil hin. Die Erhaltungstherapie bekommt einen zunehmenden Stellenwert in der Therapie des MM und kann das Gesamtüberleben verlängern. Thalidomid sollte jedoch nicht bei Patienten mit Hochrisikozytogenetik angewendet werden, da es das Gesamtüberleben verkürzt.

Zur Rezidivtherapie stehen Immunmodulatoren und Proteasominhibitoren der zweiten und dritten Generation zur Verfügung. Zum Beispiel wurde gezeigt, dass die Therapie mit Pomalidomid/Dexamethason im Vergleich zur Therapie mit hochdosiertem Dexamethason das Gesamtüberleben signifikant verlängert (12,7 vs. 8,1 Monate; p = 0,03). Daneben werden neue, ziel- und knochenmarkstromagerichtete Therapien untersucht. Insbesondere Antikörper, namentlich anti-CS1 (Elotuzumab) und anti-CD38 (Daratumumab) befinden sich in fortgeschrittenen Phase-II/III-Studien.

Abstract

The diagnosis and treatment of multiple myeloma (MM) are progressing continuously. This article aims at summarizing the current status in the diagnosis and treatment of MM, emphasizing a clinical point of view. Prognostic factors can be determined by clinical parameters, molecular analyses and patient characteristics (e.g. age and comorbidities). The international staging system (ISS) and cytogenetics, such as the high-risk aberrations 17p deletion, translocation (4;14) and insertion 1q21 > 2 copies, are key factors in risk stratification of MM patients. Induction therapy based on novel agents, namely bortezomib, followed by subsequent high-dose melphalan and autologous stem cell transplantation is considered the standard of care for younger, newly diagnosed MM patients (≤ 70 years). Transplant-ineligible patients should receive thalidomide or bortezomib-based chemotherapy. The combination of bortezomib, melphalan and prednisone (VMP) was shown to significantly improve overall survival (OS) compared to melphalan and prednisone (MP, 56.4 vs. 43.1 months, p = < 0.01). Recent results suggest that lenalidomide-based therapy not incorporating alkylating agents might be a competitive alternative with a favorable toxicity profile for transplant-ineligible patients. Maintenance therapies are of increasing clinical significance in MM as they have the ability to prolong overall survival; however, thalidomide maintenance therapy should not be used in MM patients with high-risk cytogenetics as it shortens OS. Refractory or relapsed MM treatment continues to improve with the development of second and third generation immunomodulatory agents and proteasome inhibitors. For example, pomalidomide and dexamethasone vs. high-dose dexamethasone significantly improved OS (12.7 vs. 8.1 months, p = 0.03). Novel therapy strategies include targeted and stroma-directed approaches. Antibodies targeting CS-1 (elotuzumab) and CD38 (daratumumab) in particular are currently undergoing advanced clinical phase II/III trials.

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Einhaltung ethischer Richtlinien

Interessenkonflikt. E.K. Mai weist auf folgende Beziehung hin: Reisekostenerstattung durch Fa. Janssen-Cilag. H. Goldschmidt gibt an, dass kein Interessenkonflikt besteht. Dieser Beitrag beinhaltet keine Studien an Menschen oder Tieren.

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  1. Medizinische Klinik V, Universitätsklinikum Heidelberg und Nationales Centrum für Tumorerkrankungen (NCT) Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Deutschland

    E.K. Mai &  H. Goldschmidt

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  2. H. Goldschmidt
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Correspondence to E.K. Mai or H. Goldschmidt.

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Mai, E., Goldschmidt, H. Klinik und Therapie des multiplen Myeloms. Radiologe 54, 538–544 (2014). https://doi.org/10.1007/s00117-013-2625-z

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