Visibility Of Bone Lesions In Relapsed Multiple Myeloma Can Be Improved By FDG-PET Scanning

Osseous involvement is one the predominant features of patients with multiple myeloma (MM). Whole body X-ray (WBX) is the standard method for detecting skeleton abnormalities but has limited value in relapsing disease since it cannot make a distinction between old and new active skeleton lesions. Therefore changes in metabolic activity might be a more useful method to detect new skeleton lesions in MM. This can be assessed by [F-18] fluorodeoxyglucose positron emission tomography (FDG-PET) imaging. Consequently WBX and FDG-PET was studied in relapsing MM prior to treatment. In addition immunohistochemical staining on bone marrow biopsies was performed for glucose transport protein (GLUT) 3 expression, micro vessel density (MVD), and vascular endothelial growth factor (VEGF) to demonstrate whether these parameters might be predictive for the in vivo scanning results. This study included 44 patients (median age 62 yr (range 48-78)) with a median of 3.5 (range 2-12) relapses. Thus far 86% of the patients were treated with autologous stem cell transplantation in combination with bortezomib (78%) or lenalidomide (65%). New lesions on FDG-PET were more frequently demonstrated than new lesions on WBX (p=0.00001). In 78% of the patients FDG-PET demonstrated a median of 4 lesions (range 0-22) per patient with a median standard uptake value (SUV) max of 5.7 (range 0-24). In 42% of the patients new X-ray lesions (median 0 (range 0-7)) were demonstrated and these were concordant with the results of FDG-PET. In 5 % of the patients new X-ray lesions were observed without FDG-PET lesions. For the relapsing patients treatment consisted of dexamethasone in combination with bortezomib (65%) or lenalidomide (50%). CR was obtained in 27% of the patients, PR in 39% and progressive disease in 22%. Average time to next treatment (TTNT) was 11.7 months (2-43). However FDG-PET positivity was not predictive for PFS (p =0.55) and OS (p=0.40) neither if PET positivity was defined as more than 3 lesions nor if the cut off value of SUV max > 4.2 was applied. Immunohistochemical staining on bone marrow biopsies (n=20) with CD34 demonstrated a significant increased MVD of 39 ± 54 (mean ± SD, normal bone marrow MVD 3.5 ± 2.9), in particular when clusters of plasma cells were present. These enhanced MVD was associated with a significant increased expression of VEGF and GLUT-3. However MVD (p = 0.16), VEGF (p = 0.70) or GLUT-3 (p =0.70) expression were not predictive for having a positive or negative FDG-PET. In summary, our results demonstrate that FDG-PET is more informative than WBX for detecting skeleton lesions in relapsing MM patients. However, and in contrast to what was previously shown in patients with newly diagnosed MM, FDG-PET it is not predictive for treatment outcome. This might be due to heterogeneity in studied patients and treatments.