Multiples Myelom

Was ist gesichert in der Therapie?
Schwerpunkt: Was ist gesichert in der Therapie?

Zusammenfassung

Das multiple Myelom (MM) ist eine maligne Neoplasie terminal differenzierter B‑Zellen, der Plasmazellen, und primär im Knochenmark lokalisiert. Das klinische Bild im symptomatischen Stadium des MM ist gekennzeichnet durch Osteolysen, Anämie, Nierenfunktionseinschränkung und/oder Hyperkalzämie. Liegen solche MM-bedingten Endorganschäden vor, besteht eine dringliche Therapieindikation. Darüber hinaus wird heutzutage die Therapiepflichtigkeit des MM bereits anhand von Biomarkern definiert, sodass eine Therapie vor dem Eintreten von Endorganschäden eingeleitet werden kann. Die Primärtherapie basiert auf Proteasominhibition und Immunmodulation – bei geeigneten Patienten nach wie vor in Kombination mit Hochdosischemotherapie und autologer Stammzelltransplantation. Daneben haben Radiotherapie und orthopädische Chirurgie einen festen Stellenwert in der Behandlung lokaler Skelettkomplikationen. Zur Therapie des Rezidivs wurden in Europa in den vergangenen beiden Jahren fünf neue Wirkstoffe zugelassen. Dies sind einerseits Proteasominhibitoren der zweiten Generation (Carfilzomib, Ixazomib) und andererseits Vertreter neuer Wirkstoffklassen, nämlich monoklonale Antikörper (Daratumumab, Elotuzumab) und ein Histon-Deacetylase-Inhibitor (Panobinostat). So stehen nun verschiedene Dreifachkombinationen zur Verfügung, die die etablierten Regime Lenalidomid/Dexamethason und Bortezomib/Dexamethason mit jeweils einem neu zugelassenen Wirkstoff kombinieren und zu einer signifikanten Verlängerung des progressionsfreien Überlebens führen. Das mittlere Gesamtüberleben von Patienten mit multiplem Myelom konnte seit der Jahrtausendwende bei guter Lebensqualität verdoppelt werden.

Schlüsselwörter

Proteasominhibitoren Immunmodulation Histon-Deacetylase-Inhibitoren Rezidiv Minimale Resterkrankung Monoklonale Antikörper 

Multiple myeloma

What has been confirmed in therapy?

Abstract

Multiple myeloma (MM) is a malignancy of terminally differentiated B cells/plasma cells and is primarily located in the bone marrow. Symptomatic multiple myeloma typically presents with osteolyses, anemia, reduced renal function, and/or hypercalcemia. In the case of such MM-related end organ damage, urgent systemic treatment is indicated. In order to prevent end organ damage, current guidelines now recommend treatment initiation already when certain biomarkers are met. Current first-line treatment is based on proteasome inhibition and immunomodulation. Eligible patients still benefit from the addition of high-dose chemotherapy and autologous stem cell transplantation. Radiotherapy and orthopedic interventions play an important role in the treatment of localized skeletal complications. For relapsed MM, five novel agents have been approved in Europe during the last two years. These are second-generation proteasome inhibitors (carfilzomib, ixazomib) as well as first-in-class monoclonal antibodies (daratumumab, elotuzumab) and a histone deacetylase inhibitor (panobinostat). Triple combinations based on the established regimens lenalidomide/dexamethasone and bortezomib/dexamethasone plus one of the novel agents have been shown to significantly prolong progression-free survival. Median overall survival of patients with MM has doubled since the turn of the millennium.

Keywords

Proteasome inhibitors Immunomodulation Histone deacetylase inhibitors Recurrence Minimal residual disease Monoclonal antibodies 

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Copyright information

© Springer Medizin Verlag GmbH 2017

Authors and Affiliations

  1. 1.Medizinische Klinik VUniversitätsklinikum HeidelbergHeidelbergDeutschland
  2. 2.Nationales Centrum für Tumorerkrankungen (NCT) HeidelbergHeidelbergDeutschland

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