Radiological skeletal survey or computed tomography are currently applied to assess bone diseases in patients with monoclonal plasma cell disorders. Whole-body magnetic resonance imaging (whole-body MRI) allows detecting the infiltration of clonal cells in nearly the whole bone marrow compartment even before bone destruction has occurred. Those MRI results (i.e., patterns of bone marrow infiltration) have been demonstrated to be of prognostic significance in patients with symptomatic as well as asymptomatic multiple myeloma. We have therefore analyzed the findings of whole-body MRI in 137 consecutive individuals with monoclonal gammopathy of undetermined significance (MGUS). A focal infiltration pattern was detected in 23.4% of patients. Presence and number of focal lesions as well as value of M-Protein were of independent prognostic significance for progression into a symptomatic disease requiring systemic treatment (P=0.02; P<0.0001 and P=0.0005, respectively). Lower homogeneous signal intensities in T1-weighted images were related to a physiologically higher bone marrow cellularity in younger individuals (P=0.002). We conclude that whole-body MRI identifies patients with focal accumulations of presumably monoclonal cells in bone marrow with prognostic impact concerning the risk of progression into symptomatic disease.

The aim of our study was to assess in which way different infiltration patterns of monoclonal plasma cell diseases in wholebody (wb) magnetic resonance imaging (MRI) are associated with clinical stages, plasma cell content in bone marrow samples and established serum markers of disease activity. Institutional review board approval was obtained. We performed wb-MRI in 547 consecutive, unselected and untreated patients with monoclonal gammopathy of undetermined significance (MGUS, n 5 138), smoldering myeloma (SMM, n 5 157) and multiple myeloma (MM, n 5 252) on two 1.5 T MRI-scanners with body array coils. The studies were evaluated in consensus by two experienced radiologists blinded to the diagnosis. We observed focal lesions in 23.9% (MGUS), 34.4% (SMM) and 81.3% (MM), respectively. A diffuse infiltration pattern was detected in 38.4%, 45.9% and 71%, respectively. The differences between all infiltration patterns were significant (p < 0.0001). The presence of focal lesions and the presence of a diffuse bone marrow infiltration was associated with an increased plasma cell percentage in bone marrow samples (median 22% vs. 14%, 26% vs. 10%, both p < 0.0001) and monoclonal protein concentration (median 18 g/dl vs. 13 g/dl, p 5 0.003, 20 g/dl vs. 11 g/dl, p < 0.0001). Further categorization of the diffuse infiltration patterns in wb-MRI into "salt-and-pepper," moderate and severe identified significant associations with M-protein (median g/dl for S1P/moderate/severe 23/18/25, p 5 0.04), plasma cell percentage in the bone marrow (median 25%/24%/40%, p 5 0.02), and age (median years 67/60/57, p < 0.0001). Bone marrow infiltration in wb-MRI is significantly different between the various stages of plasma cell disease and correlates well with established markers of disease activity.Monoclonal plasma cell diseases like multiple myeloma (MM), monoclonal gammopathy of undetermined significance (MGUS) and smoldering myeloma (SMM) are a group of hematologic premalignant or malignant disorders associated with monoclonal proliferation of plasma cells mainly in the bone marrow.1,2 Although MGUS, being the most common disorder of plasma cells and occurring in 2% of persons older than 50 years, has an overall annual risk of progression of only 1% per year, the rate of transformation of SMM to MM or systemic amyloidosis (AL) has been shown to be 10% per year in the first 5 years. [3][4][5][6] In the aforementioned monoclonal plasma cell disorders, the bone marrow involvement may be present in different patterns: diffuse bone marrow infiltration and focal lesions. Diffuse bone marrow infiltration is characterized by malignant plasma cells, mixed up with normal bone marrow cells, still preserving the cancellous bone structure. Focal lesions are circumscribed solid foci of plasma cells with the potential of destruction of the cancellous and cortical bone.To image these changes, plain radiographs (PRs), computed tomography (CT) and magnetic resonance imaging (MRI) are currently in routine use. 7 Although PR has been an integral part of...

2911 Background: Traditionally, anti-myeloma therapy is initiated by presence of end-organ damage defined by CRAB criteria (hypercalcemia, renal failure, anemia, and/or lytic bone lesions). Recently, several clinical trials have been initiated to evaluate the role of treatment in smoldering myeloma (SMM) patients, which by diagnostic criteria lack end-organ damage. Several studies have indicated the prognostic significance of magnetic resonance imaging (MRI) for patients with smoldering (SMM) and multiple myeloma (MM). Given that the risk of transformation from SMM to MM varies greatly, we have conducted a large retrospective clinical study, using whole-body MRI, to characterize patterns of tumor infiltration in the bone marrow among patients diagnosed with SMM. These patients were then followed longitudinally for progression to MM. Furthermore, we have expanded MRI studies to patients with monoclonal gammopathy of undetermined significance (MGUS), and have analyzed the imaging findings within established prognostic parameters of this group of patients. Methods: A total of 157 patients with SMM, 138 with monoclonal gammopathy of undetermined significance (MGUS), and 249 with MM were assessed by whole body MRI. Patients with second malignancies, amyloidosis, solitary plasmocytoma or preceding systemic treatment were excluded from the study. In patients with MGUS and SMM initiation of systemic treatment and in patients with MM, relapse after systemic therapy was defined as end point for progression free survival. For all patients we collected extensive clinical and diagnostic data. Using logistic regression, we evaluated the presence/absence of focal or diffuse signal abnormalities. Using log-rank test we defined treatment-free survival for SMM in relation to imaging results. Median follow-up was 4.0, 4.5 and 3.7 years for MGUS, SMM and MM patients, respectively. Results: In MGUS patients, focal lesions were detectable in 23.9% and a diffuse infiltration in 53%. Diffuse and focal infiltration patterns appeared independently from each other. The presence and number of focal lesions as well as a severe diffuse infiltration were statistically significant adverse prognostic factors for progression free survival. In multivariate analysis, only the number of focal lesions remained statistically significant (p=0.0005). In SMM patients, focal lesions were present in 34.4% and a diffuse infiltration pattern in 45.9%. Plasma cell percentage, a moderate diffuse infiltration (but not focal lesions) and beta2-microglobulin were statistically significant prognostic parameters. Whole-body MRI indicated that for 65.6% of the patients with SMM, patterns of tumor cell infiltration in the bone marrow were similar to MGUS patients; whereas 34.4% showed patterns similar to MM patients. Sensitivity and specificity of prediction performance of the classification model was 0.8 and 0.76, respectively. Using a log-rank test for prediction of treatment-free survival of SMM patients in relation to whole-body MRI patterns of tumor cell infiltration in the bone marrow, we found a borderline difference between MGUS-like SMM (n=124) and MM-like SMM patients (n=33) (p=0.08); whereas the difference between MM-like SMM patients and the 138 MGUS patients was significant (p=0.02). Conclusions: In summary, in this first large clinical study including 544 patients, whole-body MRI was able to discern over 30% of patients with SMM presenting with patterns of tumor cell infiltration in the bone marrow similar to those of MM. Given that many patients with SMM develop symptomatic disease within 1–2 years, in the future, advanced imaging may play a major role in defining patients with SMM who should be candidates for early treatment. Disclosures: No relevant conflicts of interest to declare.

4966 Focal lesions (FL) and diffuse tumor cell infiltration detected by whole body MRI (WB-MRI) have been demonstrated to be of prognostic significance for predicting progression free and overall survival in patients with monoclonal plasma cell diseases. In this trial we have assessed 544 unselected and untreated patients: 138 with monoclonal gammopathy of undetermined significance (MGUS), 157 with smoldering myeloma (SMM), and 249 with multiple myeloma (MM). WB-MRI was performed on two identical 1. 5 Tesla MRI-scanners with body array curls. Assessment of FL was done by two experienced radiologists blinded to the diagnosis of the patients in consensus. We found focal lesions in 23. 9%, 34. 4%, and 80. 3% of patients with MGUS, SMM and MM, respectively, and a diffuse infiltration was detected in 38. 4%, 45. 9%, 71. 5% of the corresponding patients. The differences between MGUS, SMM and MM patients were statistically significant (p<0. 0001). The presence of FL as well as the presence of a diffuse infiltration was correlated with an increased plasma cell percentage in bone marrow (p<0. 0001) and monoclonal protein concentration (p=0. 001). Further categorization of the diffuse infiltration patterns in WB-MRI into minimal, moderate, severe and “salt&pepper” patterns, was able to identify a significant correlation between both M-protein and plasma cell percentage in bone marrow as well as age. In MGUS and SMM patients, FL were more often detected in patients with a diffuse background, while in MM patients, FL were present at the same rate across the diffuse infiltration subgroups. In summary bone marrow infiltration in WB-MRI is significantly different between stages of plasma cell disease and correlates with established markers of disease activity. Disclosures: No relevant conflicts of interest to declare.