With whole-body magnetic resonance imaging (wb-MRI), almost the whole bone marrow compartment can be examined in patients with monoclonal plasma cell disease. Focal lesions (FLs) detected by spinal ...MRI have been of prognostic significance in symptomatic multiple myeloma (sMM). In this study, we investigated the prognostic significance of FLs in wb-MRI in patients with asymptomatic multiple myeloma (aMM).
Wb-MRI was performed in 149 patients with aMM. The prognostic significance of the presence and absence, as well as the number, of FLs for progression into sMM was analyzed.
FLs were present in 28% of patients. The presence per se of FLs and a number of greater than one FL were the strongest adverse prognostic factors for progression into sMM (P < .001) in multivariate analysis. A diffuse infiltration pattern in MRI, a monoclonal protein of 40 g/L or greater, and a plasma cell infiltration in bone marrow of 20% or greater were other adverse prognostic factors for progression-free survival in univariate analysis.
We recommend use of wb-MRI for risk stratification of patients with asymptomatic multiple myeloma.
In multiple myeloma, focal lesions, as well as diffuse and variegated infiltration patterns, can be detected by magnetic resonance imaging. In the current study, we compared treatment response in 100 ...myeloma patients with changes in infiltration patterns in whole body magnetic resonance imaging before and after autologous stem cell transplantation. We found an agreement between serological response and changes in imaging (P<0.001). In detail, a significant agreement of treatment response was observed for diffuse (P=0.004) as well as for focal (P=0.01) infiltration patterns. The number of focal lesions at second magnetic resonance imaging was of prognostic significance for overall survival (P=0.001). We conclude that treatment response in myeloma goes along with a decrease in imaging findings. We suggest that residual disease after high-dose chemotherapy detected by magnetic resonance imaging increases the risk of relapse. Therefore, myeloma patients with such findings after treatment might benefit from further cytoreduction.
Abstract 1812
Magnetic resonance imaging (MRI) has been demonstrated to be the most sensitive imaging technique to detect both diffuse and focal infiltration of multiple myeloma cells in bone marrow. ...Whole body magnetic resonance imaging (WB-MRI) can be applied using affordable extensions to standard MRI scanners. Recent studies have shown that the presence and number of focal lesions (FL) in MRI are of prognostic significance in symptomatic as well as smoldering multiple myeloma. The aim of the present study was to investigate the significance of persisting FL after autologous stem cell transplantation. To answer this question WB-MRI of 100 patients eligible for high dose chemotherapy with symptomatic myeloma were retrospectively evaluated before the start of systemic treatment and after single or tandem autologous stem cell transplantation. Number of FL was assessed by two investigators in consensus for each time point separately. The analysis was approved by the institutional ethics committee. Patients were classified into different groups according to the number of FL in WB-MRI. At first MRI, 24 patients presented with 0, 36 with 1–10, 13 with 11–20 and 27 with more than 20 FL. At time of second MRI 25 patients had no, 51 patients 1–10, 13 patients 11–20 and 11 patients more than 20 FL. Overall survival was defined as time from second MRI until death of any cause. MRI-response according to the change of the number of FL was defined as focal complete remission (fCR) indicating total disappearance of FL, focal partial remission (fPR) being defined as reduction of the number of FL of 50% or more, focal stable disease (fSD) as unchanged number of FL and focal progressive disease (fPD) as any increase in number of focal lesions after therapy. At second MRI an fCR was found in 25; an fPR in 22; an fSD in 26 and an fPD in 27 patients. For evaluation of prognostic significance of the number of FL for overall survival a log rank test resulted in a p-value of 0.17 for the first and 0.02 for the second WB-MRI. Kaplan-Meier plots for overall survival according to the number of FL at first and second MRI are shown in Figure 1 and 2 respectively. Number of FL was not of prognostic significance for progression free survival (p = 0.6 and p = 0.8 for first and second MRI respectively). Serological and MRI-defined response concerning FL were significantly associated (p = 0.003; Kendall’s Tau 0.26) with a trend to an underestimation of response in FL compared to serological response. The fact that the number of FL after high dose chemotherapy but not at first diagnosis of symptomatic myeloma had a significant impact on survival in our study confirms the importance of the measurement of residual disease after systemic treatment as it has been demonstrated for methods as flow cytometry and others. Thereby WB-MRI allows the evaluation of nearly the whole bone marrow compartment non-invasively and without the need of irradiation exposure. A limitation of MRI is the fact that it is not capable of differentiating between FL containing vital tumor cells and those representing osteolyses without active myeloma. New functional MRI sequences like dynamic contrast-enhanced MRI and diffusion weighted imaging may overcome this disadvantage. Furthermore, positron emission tomography has been demonstrated to be another possibility for detection of residual disease activity after therapy. Further studies will show which imaging technique is most useful in myeloma or if different clinical and scientific questions necessitate different methods. Display omitted Display omitted
Goldschmidt:Janssen-Cilag: Consultancy; Celgene: Consultancy; Millennium Pharmaceuticals, Inc.: Consultancy.
Abstract 2977
Findings of magnetic resonance imaging (MRI) are increasingly being applied to assess disease activity and tumor mass in patients with multiple myeloma (MM), since it has been shown ...that this technique is the most sensitive to detect bone marrow infiltration in monoclonal plasma cell disease. However, the correlation of serological response to systemic treatment with alterations in MRI has not been investigated. We therefore analyzed changes in diffuse infiltration and in number and size of focal lesions (FL) in whole body-MRI (wb-MRI) in 100 patients after systemic therapy in order to learn whether the degree of remission would differ for morphological, MRI-based and serological criteria. Median age of patients was 59 years (range 28–74 years). Autologous stem cell transplantation was performed in 93, and conventional chemotherapy including novel agents in 7 patients. MRI protocol included T1 and T2 weighted sequences in coronal orientation of the whole body (excluding T2 of the lower legs to maintain acceptable examination time) as well as T1 and T2 weighted sequences of the whole spine in sagittal orientation. MRI-remission was assessed by two experienced radiologists in consensus for focal and diffuse infiltration separately and in combination. Definitions of MRI-response were determined with focal complete remission (fCR) indicating total disappearance of focal lesions, focal partial remission (fPR) being defined as reduction of the number of FL of 50% or more, focal stable disease (fSD) as unchanged number of FL and focal progressive disease (fPD) as any increase in number of focal lesions after therapy. For diffuse infiltration dCR was defined as total disappearance of diffuse infiltration. If diffuse infiltration was reduced after therapy but was still detectable in MRI it was defined as dPR. Constancy of diffuse infiltration was defined as dSD and increase in diffuse infiltration as dPD. Serological remission was determined summarizing near CR and CR as seroCR and VGPR and PR as seroPR to simplify statistical analysis.
A weak but significant correlation of MRI-derived with serological remission was found for focal response with a correlation coefficient (CC) of 0.26 and a p-value of 0.003 and for diffuse response with a CC of 0.27 and a p-value of 0.003 respectively. In diffuse infiltration the remission stage would be more favorable if determined with MRI than with serological criteria, whereas in focal or multifocal disease patterns serological criteria would indicate a better response than would MRI changes. However, these differences were not significant. In contrary to a recent publication of the Arkansas group no better progression free survival (PFS) was seen for patients with more favorable MRI-response. Comparison of the 8 out of 40 patients in serological CR or near CR who also achieved a MRI-CR showed no significantly better PFS compared to patients in whom serological CR was achieved but residual infiltration was detected in MRI.
We conclude that serological response to chemotherapy goes along with a similar trend of changes in MRI after systemic chemotherapy. The fact that the correlation in our study was rather weak and no survival benefit was found for MRI-CR, may be at least in part due to the inability of conventional MRI to differentiate between vital lesions and residual changes after treatment as well as between plasma cell infiltration and increased cellularity because of bone marrow regeneration after chemotherapy. Furthermore, residual lesions may consist of hyposecretory myeloma cells which can eventually lead to relapse of disease. Functional imaging methods such as positron emission tomography and new MRI techniques e.g. dynamic contrast-enhanced MRI and diffusion weighted imaging may contribute to solve these questions. If treatment of residual changes in MRI for example by local irradiation leads to a better outcome by deepening remission is another issue arising from our results.
No relevant conflicts of interest to declare.
Abstract 4868
In magnetic resonance imaging (MRI) multiple myeloma (MM) presents with circumscribed focal lesions or diffuse infiltration of bone marrow. To identify genetic mechanisms influencing ...the growth pattern, whole-body MRI of 99 patients with asymptomatic and 114 patients with symptomatic MM were evaluated retrospectively by two experienced radiologists. The pattern was analyzed in the spine and focal lesions were counted in the whole body differentiating intra-osseous and soft tissue lesions as well as osseus tumors affecting cortical bone. Cytogenetic analysis was performed using interphase fluorescence in-situ hybridization (iFISH) on CD138-purified monoclonal plasma cells acquired by unilateral bone marrow aspiration for the following aberrations: t(4;14), t(11;14), t(14;16), deletions 13q14 and 17p13, as well as gain of 1q21. Statistical analysis was performed to address the following questions: i) Is there a significant correlation of chromosomal abnormalities with the presentation of MM in MRI ii) Is there an association of the occurrence of affection of cortical bone with cytogenetic aberrations. As a number of more than 7 focal lesions in the axial skeleton has been shown to be an adverse prognostic factor for patients with symptomatic MM, we performed a search for an optimal cut-off point in number of focal lesions in whole body MRI with respect to progression free survival and overall survival. As event for progression free survival initiation of treatment for asymptomatic MM and progression after the first line of treatment for symptomatic MM was defined.
Correlation of the presentation of MM in MRI with common chromosomal abnormalities was found neither concerning focal or diffuse infiltration patterns nor an affection of cortical bone, potentially leading to instability.
A search for the optimal cut-off point led to a number of more than one and more than 8 focal lesions in whole body MRI for asymptomatic and symptomatic MM respectively.
The only significant prognostic factors for progression of asymptomatic MM into symptomatic disease were the presence per se and a number of more than one focal lesion or diffuse infiltration in MRI. For symptomatic myeloma a number of more than 8 focal lesions was the only significant prognostic factor for overall survival (HR 4.87; p-value <0.001). In symptomatic disease the factors t(4;14), gain of 1q21 and a diffuse infiltration pattern (for overall survival) and gain of 1q21 (for progression free survival) lost statistical significance after adjustment of p-values because of multiple testing.
In our cohort of 213 patients the most important risk factors for overall survival were focal lesions above a cut-off point of 1 and 8 for asymptomatic and symptomatic MM, respectively. No correlation of the appearance of MM in MRI with the presence of cytogenetic abnormalities in iFISH analysis was found. We therefore conclude that the infiltration pattern in MRI is not associated with cytogenetic abnormalities and that the number of focal lesions in whole body MRI is an important and independent risk factor for patients with multiple myeloma.
No relevant conflicts of interest to declare.
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