"WB-DCE-MRI" in Multiple Myeloma as an Independent Prognostic Factor for Disease-free Survival
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Study type: Interventional

Summary: 
      The main objective of this study is to examine if absence of a satisfactory response on
      DCE-WB-MRI (see MR criteria of responders section) after completion of HDT followed by
      autologous stem-cell transplantation (ASCT) is an independent prognostic factor for EFS in
      patients with MM, compared with established ones including beta2-microglobulin and
      cytogenetic abnormalities. Secondary objectives are to examine if the microcirculation
      parameters obtained from baseline DCE-WB-MRI have prognostic significance and to examine if
      early DCE-WB-MRI performed after the induction HDT and before ASCT might also provide
      independent prognostic information for patient outcome, which might help in patient
      stratification and be integrated into the response criteria in the future.
    

Detailed description: 
      Introduction Bone marrow angiogenesis is increased in multiple myeloma (MM) and is an
      important prognostic factor for survival. Newly diagnosed MM patients have higher microvessel
      density (MVD) than controls on bone marrow biopsies. In addition, patients with higher MVD,
      receiving conventional chemotherapy or high-dose therapy with autologous stem cell
      transplantation, have shorter median overall survival than those with lower MVD by using the
      median MVD as the cutoff. In a study with 81 patients with MM treated with thalidomide with
      or without dexamethasone, MVD decreased significantly in responders while no significant
      change in MVD was seen in those failing to respond to thalidomide.

      Microcirculation variables derived from dynamic contrast-enhanced magnetic resonance (DCE-MR)
      imaging, i.e. maximum enhancement and the exchange rate constant, correlate well with the
      histologic infiltration grade, MVD and serum markers of disease activity. Recently, the
      maximal amplitude of lumbar bone marrow enhancement on DCE-MR examination has been identified
      as a prognostic variable for event-free survival (EFS) in progressive MM. These parameters
      may serve as non-invasive surrogate biomarkers for determining prognosis and for assessing
      treatment response in myeloma patients. However, these studies used techniques which were
      limited to a maximal 400-mm field of view, whereas myeloma can involve the bone marrow
      focally, diffusely throughout the body, or even outside the marrow space. With the
      advancement of MR technologies, unenhanced whole-body MR imaging has proven more reliable
      than radiological skeletal survey and whole-body multidetector computed tomography in
      patients with MM.

      Recently, whole-body single-phase contrast-enhanced sequence was applied in combination with
      unenhanced sequences for the detection of myeloma lesions. However, single-phase
      post-contrast MR examinations do not provide detailed enhancement curves, and this limitation
      possibly hinders the assessment of disease activity. On the other hand, segmental dynamic MR
      examinations do not enable assessment of the dynamic enhancement of focal lesions in
      different bone marrow segments. That was the reason which led us to develop a dynamic
      contrast-enhanced whole-body magnetic resonance imaging (DCE-WB-MRI) protocol, which was
      never explored in MM.

      The treatment of patients with MM was largely palliative until, with the advent of high-dose
      melphalan, high rates of complete response (CR) could be obtained. For previously untreated
      patients aged 70 years (amendment n°5)or younger, high-dose therapy (HDT) followed by
      treatment (amendment n°3) with growth-factor-mobilized peripheral-blood stem cells (PBSCs)
      have been demonstrated superior to conventional chemotherapy with not only higher CR rates
      but also significantly extending EFS and overall survival. Recently, the International
      Myeloma Working Group proposed new uniform response criteria to facilitate precise
      comparisons between new evolving treatment strategies. As a functional imaging providing
      parameters related to angiogenesis and disease activity in MM, DCE-WB-MRI might provide
      additional information on prognostically important microcirculation variables on a whole-body
      scale. It might also prove helpful in assessing treatment response and further treatment
      strategy decision for patients with oligo- or nonsecretory disease.

      Study Description :

      Treatment regimen: the HDT followed by ASCT with PBSCs will be given. The ASCT will be
      conditioned by high-dose melphalan (HDMel) 200 mg/m2 with or without bortezomib following the
      actual guidelines.

      Response assessment: clinical response will be assessed on the same day of each
      post-treatment MR examination and recorded according to the uniform response criteria. After
      completion of HDT followed by ASCT, patients will be followed every 4 months for the first
      two years and every 6 months thereafter for a total of at least 5 years. An event is defined
      as disease progression, relapse from clinical CR/VGPR, or death from any cause.

      DCE-WB-MRI schedule: three MR examinations will be performed, the first at diagnosis and
      before initiation of chemotherapy, the second after induction chemotherapy and before ASCT,
      and the third exam three months after ASCT. The results of each DCE-WB-MRI will not influence
      further treatment strategy.

      MR Criteria of Responders:

      A satisfactory response on DCE-WB-MRI is defined by the presence of a maximal percentage of
      bone marrow enhancement below 100%. All focal lesions, if present, must not present an early
      enhancement but a progressive, delayed type maximal enhancement.
    

Intervention name(s): Whole Body Dynamic Contrast Enhanced MRI (WB-DCE-MRI)
Intervention type(s): Device
Intervention description(s): 3 Whole Body Dynamic Contrast Enhanced MRI:
1 WB-DCE-MRI before induction of chemotherapy(initial MRI).
1 WB-DCE-MRI after induction high dose therapy and before intensification of chemotherapy and auto-transplant of hematopoietic sterns cells (early MRI).
1 WB-DCE-MRI 3 months after treatment whatever (amendment n°3) (delayed MRI).
Other intervention name(s): Mult.Myeloma eligible for Autologous Stem Cell Transpl.
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Diagnostic
Keywords: multiple myeloma; Autologous Stem Cell Transplantation