Prognostic value of bone disease in MM, an evaluation of different imaging techniques at diagnosis and in follow-up.

Bone disease, defined as osteolytic lesions and osteoporosis, is common in patients with symptomatic/stage III Multiple Myeloma (MM), with up to 90% of patients developing bone lesions and up to 60% of patients experiencing a pathologic fracture in the course of the disease.

The sensitivity of conventional WBXR analysis is low, given that at least 30% of trabecular bone substance must be lost in order to give rise to visible lytic lesions. Recently, other imaging modalities including WB-MRI and FDG-PET-CT have become available, which in general are more sensitive than WBXR. Although the negative prognostic impact of the presence of bone lesions as detected by WBXR is clear and has been validated in differently treated patient populations, there is less information on the prognostic value of baseline MRI and even more sparse data concerning the other imaging techniques. Therefore it is necessary to investigate the prognostic impact of these newer imaging techniques before replacing WBXR.



Currently, bone Currently remission status is being performed according to the IMWG criteria, measuring m-protein levels and clonal plasmacell counts. Bone disease as indicated by WBXR is only being monitored to exclude progression, as generally no responses can be observed. Based on earlier research it is suggested that normalization of bone disease detected by newer imaging was prognostic importance. It is not clear which imaging technique is most suitable for respons evaluation.



Therefore every patient will undergo WB-MRI and FDG-PET-CT before start of treatment and after the third and ninth chemotherapy cours this will be repeated in half of the included patients.

Primary objective:

1. To assess the prognostic value of MM related bone disease as detected by FDG-PET in terms of progression free survival;

2. To determine the conversion rate, defined as complete normalization, of FDG-PET-CT, after 3 cycles and completion of therapy [part II only].



Secondary objectives:

1. To assess the prognostic value of MM related bone disease as detected by WBXR, WB-MRI and CT in terms of progression free survival;

2. To assess the prognostic value of MM related bone disease as detected by WBXR, WB-MRI, CT and FDG-PET in terms of clinically symptomatic bone disease;

3. To assess the prognostic value of MM related bone disease as detected by WBXR, WB-MRI and FDG-PET-CT in terms of overall survival;

4. To compare the number and distribution of lesions detected by WBXR, WB-MRI and FDG-PET-CT;

5. To assess the relation between the extent of MM related bone disease detected by WBXR, WB-MRI and FDG-PET-CT and biological features of MM bone disease as determined by DKK1 levels, sRANKL and osteoprotegerin;

6. To investigate distinct patterns of gene expression involved in MM related bone disease;

7. To determine the conversion rate, defined as complete normalization, of WB-MRI and contrast-enhanced MRI and diffusion-weighted MRI, after 3 cycles and completion of therapy [part II only];

8. To compare the response rate as determined by imaging techniques with classical response monitoring according to IMWG [part II only];

9. To assess and compare the prognostic value of mid- and post-treatment remission status as determined with imaging techniques and classical response monitoring in terms of PFS and OS [part II only];

10. To compare “classical” MRI with contrast-enhanced MRI and diffusion-weighted MRI with respect to focal lesions and diffuse infiltration by multiple myeloma [part II only].

1. Diagnosis;

2. 3 months (after 3th cycle of chemotherapy);

3. 9 months (after 9th cycle of chemotherapy).

1. FDG-PET-CT before treatment (60 patients) in follow up after 3th and 9th chemotherapy cycle (30 patients);

2. MRI before treatment (60 patients) in follow up after 3th and 9th chemotherapy cycle (30 patients);

3. Questionnaires before treatment (60 patients) in follow up after 3th and 9th chemotherapy cycle (30 patients);

4. OPG, sRANKL and DKK-1 before treatment in follow up after 3th and 9th chemotherapy cycle .