Multiples Myelom – aktuelle Standards in Diagnostik und Therapie

Zusammenfassung

Hintergrund Das multiple Myelom (MM) ist als maligne hämatologische Systemerkrankung nach Einteilung der Weltgesundheitsorganisation (WHO) dem Formenkreis der Plasmazellneoplasien zuzuordnen. Die weltweite Inzidenzrate des MM liegt etwa bei 6 – 7/100 000 Einwohnern/Jahr und macht somit etwa 1% aller Krebserkrankungen der Welt aus. In Deutschland sind ca. 6000 Neuerkrankungen pro Jahr zu verzeichnen. Im Zeitalter der sog. neuen Therapiesubstanzen wie Immunmodulatoren, Proteasomeninhibitoren und Antikörpern haben sich in der Behandlung des MM enorme Fortschritte ergeben. Auf dem Fachgebiet der Orthopädie und Unfallchirurgie ist es von großer Bedeutung, die Leitsymptome des MM im klinischen Alltag sicher zu erkennen und durch eine zielgerichtete Basisdiagnostik weiter abzuklären. Die operative Versorgung von myelomassoziierten Skelettläsionen, wie etwa die Stabilisierung von pathologischen Frakturen, ist Aufgabe der orthopädischen Chirurgie.

Methoden Auf Grundlage einer umfassenden Literaturrecherche, die selektiv in PubMed mit den Stichworten „multiple myeloma“ and „diagnostic“ or „therapy“ erfolgte, wurde die verfügbare Primär- und Sekundärliteratur zu aktuellen Standards in der Diagnostik und Therapie des MM beurteilt. Eingeschlossen wurden systematische Reviews, Metaanalysen, klinischen Studien und internationale Therapieempfehlungen bis Frühjahr 2016.

Ergebnisse Es existieren heute sehr sensitive Nachweismethoden in der Diagnostik des MM, die neben der bildgebenden Skelettdiagnostik und histologischen Knochenmarkuntersuchung insbesondere die klinisch-chemische Serum- und Urindiagnostik, einschließlich eines 24-h-Sammelurins umfassen. Nach heutigem Kenntnisstand besteht das therapeutische Grundkonzept aus der Kombination einer Hochdosischemotherapie (HDT) und einer autologen Blutstammzelltransplantation (ASCT). Die einzelnen Therapiesäulen der meist multimodalen Behandlungsstrategie sind in enger fachübergreifender Zusammenarbeit patientengerecht abzuwägen. Hierbei ist für die Bewertung des Risikoprofils des Patienten das Lebensalter, die Komorbiditäten sowie der individuelle Krankheitsverlauf (Rezidivneigung oder therapierefraktäre Krankheitsprogression) zu berücksichtigen. Bei Patienten > 70. – 75. Lebensjahr und/oder schweren Komorbiditäten, für die eine HDT und ASCT i. d. R. ungeeignet ist, müssen Indikationen für konventionelle Therapieoptionen gestellt werden. Darüber hinaus sind supportive Behandlungsmaßnahmen wie die Gabe von Bisphosphonaten zur Knochenprotektion, stabilisierende Operationen von pathologischen Frakturen oder eine lokale Strahlenbehandlung von schmerzhaften Osteolysen in das gesamtheitliche Therapiekonzept des MM einzubinden.

Schlussfolgerung In aktuellen Studienuntersuchungen konnte gezeigt werden, dass neue Wirkstoffgruppen wie Proteasomenhemmer, immunmodulatorische Substanzen und Antikörper bereits vielversprechend in der Behandlung des MM eingesetzt werden können, um die Prognose und Lebensqualität von Myelompatienten in Zukunft weiter zu verbessern. Hierbei werden die Therapiealgorithmen komplexer und kostenintensiver.

Abstract

Background Multiple myeloma is a haematological blood cancer of the bone marrow and is classified by the World Health Organisation (WHO) as a plasma cell neoplasm. In multiple myeloma, normal plasma cells transform into malignant myeloma cells and produce large quantities of an abnormal immunoglobulin called monoclonal protein or M protein. This ultimately causes multiple myeloma symptoms such as bone damage or kidney problems. The annual worldwide incidence of multiple myeloma is estimated to be 6 – 7/100,000 and accounts for 1% of all cancer. In Germany, there are about 6,000 cases of newly diagnosed multiple myeloma per annum. In the current era of new agents, such as immunomodulatory drugs and proteasome inhibitors and antibodies, enormous progress has been achieved in the therapy of multiple myeloma. In orthopaedics, it is essential to be able to recognise the of alarming symptoms of multiple myeloma in clinical routine and to be aware of basic diagnostic features to confirm this disease. Surgical treatment of myeloma-related bone lesions – such as stabilisation of pathological fractures – is an important domain of tumour orthopaedic surgery.

Methods A comprehensive literature search was performed in PubMed using the keywords “multiple myeloma” and “diagnostic” or “therapy”. This served to evaluate the available primary and secondary literature on the current status of the diagnostic testing and therapy of multiple myeloma. Systematic reviews, meta-analyses and clinical studies as well as international recommendations in therapy were included until the spring of 2016.

Results There are now very sensitive screening methods for the diagnosis of multiple myeloma. Accurate diagnosis is generally based on several factors, including physical evaluation, patient history, symptoms, and diagnostic testing results. The standards for initial diagnostic tests are determined by blood and urine tests as well as a bone marrow biopsy and skeletal imaging, such as X-rays, CT scans and MRI scans. Major and minor criteria are required to confirm the diagnosis of multiple myeloma and help to determine the classification and staging of multiple myeloma, and whether it is smoldering myeloma (asymptomatic), symptomatic myeloma, or a monoclonal gammopathy of undetermined significance (MGUS). Multiple myeloma treatment options have increased significantly over the last 10 years. Standard of basic myeloma treatment consists of high dose chemotherapy in combination with autologous stem cell transplantation. Several factors may determine multiple myeloma treatment, such as age and general health, results of laboratory and cytogenetic (genomic) tests as well as symptoms and disease complications. After evaluation of these factors, an individual and often multimodal treatment plan is created and implemented in interdisciplinary cooperation. Conventional treatment options have to be evaluated for older patients (> 70 – 75 years), who are not eligible for high dose chemotherapy and autologous stem cell transplantation due to their age and/or severe comorbidities. It is essential to include supportive therapy in the integral treatment concept, in order to control pain or retain function or mobility. Supportive drugs such as bisphosphonates but also radiation therapy and orthopaedic surgery may be required in order to manage complications of the disease as well as side effects of treatment.

Conclusion Current studies show promising results in the treatment of multiple myeloma, due to new agents such as immunomodulatory drugs, proteasome inhibitors and antibodies, which may improve prognosis and survival rate among myeloma patients in the future. However treatment algorithms have become more complex and expensive.

Schlüsselwörter

multiples Myelom - aktuelle Diagnostik- und Therapiestandards - neue Proteasomenhemmer - neue immunmodulatorische Substanzen - Antikörper

Key words

multiple myeloma - current status in diagnostic and therapy - new immunomodulatory drug/proteasome inhibitor - antibodies

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