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01. September 2020
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Supportivtherapie

Bei Patienten mit behandlungsbedürftigem Myelom und Knochenbeteiligung (ca. 90% aller Patienten) (40, 151, 152) ist eine Bisphosphonat-Therapie Standard. Sie sollte parallel zur Chemotherapie eingeleitet werden. Hierdurch können die mit der Erkrankung assoziierten Komplikationen wie Frakturen, Querschnittssymptomatik und Hyperkalzämie verhindert bzw. reduziert werden. Aufgrund der derzeitigen Datenlage ist Zoledronat bei der Myelomerkrankung das Bisphosphonat der Wahl, da es dem Clodronat/oralen Bisphosphonaten hinsichtlich der Effektivität überlegen ist. Die Langzeittherapie mit Bisphosphonaten (z.B. Zoledronat 4 mg monatlich i.v.,-Pamidronat 30-90 mg monatlich i.v.) ist bei Knochenbeteiligung indiziert und führt zu einer Reduktion von Wirbelkörperfrakturen und Schmerzen. In der MRC-Myeloma IX-Studie konnte für Zoledronat über den supportiven Effekt hinaus eine Lebensverlängerung von 5,5 Monaten gezeigt werden. Die intravenöse Gabe von Aminobisphosphonaten ist zurzeit die etablierte Applikationsform, wobei die Infusionsdauer je nach Bisphosphonat deutlich unterschiedlich ist (26, 34, 153).
 
Obwohl Bisphosphonate als gut verträglich gelten, können Kieferosteonekrosen als seltene Komplikation entstehen. Es besteht ein Zusammenhang mit der Zahnhygiene. Die Deutsche Gesellschaft für Zahn-, Mund- und Kieferheilkunde (DGZMK) hat diesbezüglich ausführliche Empfehlungen publiziert. Vor Beginn einer Therapie mit Bisphosphonaten sollte der Zahnstatus überprüft und ggf. eine Sanierung erfolgen. Auf eine gründliche Zahn- und Zahnfleischpflege sind die Patienten hinzuweisen (154).
 
Zur Knochenprotektion wurden auch alternative Substanzen geprüft, z.B. Inhibitoren des Rank-Liganden (z.B. Denosumab). In einer großen Phase-III-Studie bei neu diagnostizierten MM-Patienten erwies sich Denosumab als gleich effizient wie Zoledronat in Bezug auf Skelettkomplikationen und OS mit einem geringen Vorteil beim PFS. Die Zulassung beim MM wurde deshalb erteilt (151). Die derzeit verfügbaren Substanzen zielen auf die Hemmung der Osteoklasten. Ideal wären zukünftig Wirkstoffe, die Osteoklasten-Inhibition und Osteoblasten-Stimulation kombinieren.
 
Der Einsatz von Erythropoetin kann individuell erwogen werden. Insbesondere bei persistierender Niereninsuffizienz oder unzureichendem Ansprechen auf eine spezifische Therapie kann durch Erythropoetin ein positiver Beitrag zur Lebensqualität erzielt werden. Gegen den Einsatz von Erythropoetin spricht das damit verbundene erhöhte Risiko bezüglich thromboembolischer Ereignisse. Dies ist speziell bei einer Therapie mit IMiDs und einem längerfristigen Einsatz von Steroiden zu bedenken; darüber hinaus geht das MM aufgrund der durch das Paraprotein erhöhten Viskosität mit einem erhöhten Thromboserisiko einher. Ebenso relevant für das Thromboserisiko ist die Einschränkung der Mobilität durch Schmerzen oder bei pathologischen Frakturen.
 
Tab. 6: MM-Bisphosphonat-Therapie. BP=Bisphosphonat, DR=Dosisreduktion, NI=Niereninsuffizienz
MM-Bisphosphonat-Therapie

 
Die Substitution mit Erythrozyten-Konzentraten erfolgt ebenfalls auf individueller Basis. Die Indikation ergibt sich aus dem Vorliegen von Anämiesymptomen oder einem speziellen kardialen Risikoprofil (z.B. koronare Herzerkrankung, chronische Myokardinsuffizienz). Andere Supportivmaßnahmen, wie Infektprophylaxen, i.v.-Immunglobulin-Gabe und Impfungen, sowie Details zur sicheren Bisphosphonat-Gabe sind in Tabelle 6 (1, 4, 34, 84, 153) und Empfehlungen zur Supportion und Kontrollen in Tabelle 7 zusammengefasst.
 
Tab. 7: Supportivmaßnahmen beim MM (mod. nach (1, 74-79)). SPM=secondary primary malignancies (sekundäre Malignome), B=Bortezomib, Len=Lenalidomid, Thal=Thalidomid, LMW=low molecular weight (Niedermolekulares Heparin), Dex=Dexamethason
Supportivmaßnahmen beim MM

 
Es besteht kein Interessenkonflikt.

 
Monika Engelhardt
Prof. Dr. med. Monika Engelhardt
 
Klinik für Innere Medizin I
Hämatologie, Onkologie und Stammzelltransplantation
Interdisziplinäres Tumorzentrum
Hugstetter Straße 53
79106 Freiburg
 
E-Mail: monika.engelhardt@uniklinik-freiburg.de
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