Therapie

VDT-ASCT

Ersttherapie - Patient für Transplantation geeignet

Kriterien:
  • < 70 Jahre keine Komorbiditäten, die eine Transplantation verhindern
  • Patient zwischen 70 + 75 mit Fragility Score = FIT

Therapielinien:

3 Therapielinien stehen uns zur Verfügung - Zulassung ja:

 

VDT Therapielinie - Zulassung ja

 

Therapielinie 3 - VDT-ASCT:

  • hohe Fallzahlen in der Literatur als isolierte Ersttherapie Superiority of bortezomib, thalidomide, and dexamethasone (VTD) as induction
    pretransplantation therapy in multiple myeloma: a randomized phase 3
    PETHEMA/GEM study
  • mögliche Nebenwirkungen:
              • PNP
              • Panzytopenierisiko gering
              • Steroiddiabetes

  • Velcade 1.3 mg/m2 sc, Tag 1, 4,8, and 11
  • thalidomide 200 mg daily (escalating doses in the first cycle: 50 mg on days 1 to 14, and 100 mg on days 15 to 28)
  • dexamethasone 40 mg orally on days 1-4 and 9-12
  • WH Tag28

Zyklus 1

  • Tag1 - Myelomprofil im Rahme der Diagnose - Blutabnahme nicht zwingend
  • Tag 4,8,11 - Routinelabor um Nebenwirkungen zu erfassen
  • Bestimmung der Antikörper oder M-Gradient nicht erforderlich

Zyklus 2-4

bei fehlenden wesentlich pathologischen Parametern am Tag 4+11 keine Blutabnahme
bein jedem Besuch - Nebenwirkungen? - PNP,cardial,GIT,Exanteme,Zoster..

Tag 1 Myelomprofil + M-Gradient Serumelphor + Harnuntersuchung

Responsebeurteilung nach 4 x VDT + Endoxanpriming vor ASCT

  • Myelomprofil - MGradient,LK-Ratio,Immunfixation, Harnuntersuchung
  • Skelett-Rö
  • MR Wirbelsäule und Becken
  • Knochenmarkbiopsie
  • Herzultraschall
  • bei - ASCT
  • bei Progression alternative Therapie

 

 

Vorteile

  1. Patient mit genetischem Risikoprofil

            • phase 3 study of VTD induction and consolidation therapy plus double ASCT, PFS curves were almost identical regardless of the presence or absence of t(4;14). In an additional study, incorporation
              of VTD into double ASCT as part of both induction and consolidation therapy and as post-ASCT maintenance therapy resulted in improved CR duration, PFS, and OS for the gene expression profile-defined high-risk subgroup of patients carrying the MMSET/FGFR3 hybrid transcript

  2. NINS
            • Neither thalidomide nor bortezomib is excreted through the kidneys, and dose adjustments are not required for patients with renal impairment.

 

Nachteile

  1. PNP
            • Thalidomide-induced PN is more frequently sensory or sensorimotor, is dose-dependent (more prevalent with doses higher than 200 mg/day) and duration-dependent (more likely to occur after 6-12 months).

            • Bortezomib induced PN is predominantly sensory, although in10% of cases motor neuropathy has been reported. Unlike neurologic toxicity associated with thalidomide, neuropathic pain, mainly located in
              the fingertips and toes, is a major problem with bortezomib
            • Notably, compared with single-agent bortezomib short-term use of combined bortezomib and thalidomide was not associated with a major increase in the frequency of any grade and grade 3 or 4 PN.

  2. Hypothyroidism
            • is an additional important adverse event associated with long-term therapy incorporating thalidomide.