The prognostic importance of the presence of more than one focal lesion in spine MRI of patients with asymptomatic (smoldering) multiple myeloma

Abstract

Patients with asymptomatic multiple myeloma (AMM) are at risk for development of symptomatic disease requiring therapy, at the rate of about 10% per year, in the first 5 years after diagnosis. However, while some patients with AMM have a relatively low risk approaching that of monoclonal gammopathy of undetermined significance, there is a subset of patients with AMM at very high risk for imminent development of disease complications (that is, within 1–2 years after diagnosis). Such complications may include bone fractures (commonly vertebral compression fractures) or acute renal injury and renal insufficiency, which increase the morbidity and mortality of MM patients. Currently, it is recommended that patients with AMM should be followed closely without therapy; however, a recent clinical trial indicated that for patients at high risk for progression, early intervention may be beneficial. Thus, for these ‘high-risk’ patients early intervention is now indicated by many experts, in order to avoid catastrophic complications of the disease. Nevertheless, the identification of high-risk patients is challenging and requires the consideration of several different disease characteristics. The Mayo Clinic group recently identified that patients with extensive BM infiltration (⩾60%) or with extremely abnormal free light chains (FLC) ratio (4100) are at very high risk for imminent progression within o2 years from the diagnosis of AMM. Our group has also confirmed that the above risk features identify a subset of patients with AMM at very high risk for progression, within 12–18 months from diagnosis. The Spanish group has proposed more sophisticated criteria, which require high-quality, flow cytometric analysis. In view of the need for widely available methods to identify high-risk patients, imaging studies may offer significant information. Moulopoulos et al. has published since the 90s the prognostic importance of spine magnetic resonance imaging (MRI) for patients with symptomatic and asymptomatic MM. Hillengass et al. published data indicating that patients with more than one focal lesion in whole-body MRI are at high risk for progression to symptomatic disease; however, whole-body MRI is not widely available. Our group also identified abnormal spine MRI (with either a focal or a diffuse pattern) as a factor associated with a high risk of progression to symptomatic MM. Recently the SWOG S0120 study also identified focal lesions in spine MRI as a predictor of disease progression. Thus, it is now increasingly recommended that spine MRI should be considered in the initial workup of patients with AMM with high-risk features and that patients with more than one focal lesion should be considered for early intervention. Herein, we present data from our database of patients with AMM with available spine MRI at diagnosis and with mature follow-up, in order to evaluate the prognostic importance of the presence of focal lesions in spine MRI for the identification of patients with AMM at high risk of progression. We analyzed the outcomes of 67 patients with AMM and a minimal follow-up of 2.5 years. An experienced radiologist in the field of MM (LM) reviewed all the MRIs using standard criteria. The median age of the patients was 63 years (range 35–88), 63% had immunoglobulin G and 37% immunoglobulin A MM. The median BM infiltration in trephine biopsy was 20% (range 11–90%) and 9% had ⩾ 60% plasma cells. All patients had more than 10% plasma cells probably due to the availability of BM trephine biopsy and immunohistochemistry in all of them. The median serum M-spike was 1.9 g/dl, with 48% having 42 g/dl and 11% having ⩾ 3 g/dl, a figure that is smaller than the one reported in the Mayo Clinic series. Median FLC ratio (involved to uninvolved FLC) was 7.6 (range 1–219) and 11% had FLC ratio ⩾100. After a median follow-up of 4 years (range 2.5–11 years), 21 (31%) patients have progressed to symptomatic MM and the 1-, 2and 3-year rate of progression to symptomatic MM for the cohort is 13%, 21% and 29%, respectively, with an estimated median time to development of symptomatic MM of 70 months. At the time of diagnosis 13 (20%) patients had abnormal findings in their MRIs of the spine: 9 (14%) had more than one focal lesion (FL), while 2 had diffuse pattern without focal lesions; 2 patients had only one focal lesion and were excluded from further analysis. Median time to symptomatic MM for patients with more than one focal lesion was 15 months (95% confidence interval 6–26 months), while it exceeded 5 years for patients with no focal lesions (Po0.001), corresponding to a hazard ratio of 7.2 (95% confidence interval 3–18) (Figure 1). For patients with more than one FL the 1-year progression to symptomatic MM rate was 44%, the 2-year progression rate was 69% and the 3-year progression to MM rate was 85%. The respective 1-, 2and 3-year progression rates for those with no FLs was 8%, 13% and 22%, respectively. We applied previously defined features associated with a high risk of progression (BM infiltration ⩾ 60%, FLC ratio 4100) along with the presence of more than one FL in spine MRI, and 85% of our patients had none of these risk factors and 15% had at least one. Among patients with more than one focal lesion, 6 (67%) had at least one of the other high-risk features, but in three it was the only high-risk feature. Median time to progression for those with none vs those with at least one high-risk feature was 45 years vs 9 months (Po0.001), 1-year progression rate was 4% and 60%, 2-year progression rate 11% and 71% and 3-year progression rate 21% and 89%, respectively. Our data support the prognostic importance of the MRI of the spine as a tool for the identification of patients at high risk for progression to symptomatic disease. Our results are in accordance with those reported by Hilengass et al., according to which patients with more than one focal lesion had a median time to progression of 13 months while for those without focal lesion or with one focal lesion the time to progression exceeded 5 years. In the SWOG S0120 study the presence of more than one focal lesion was associated with increased risk of disease progression in the subset of patients with available MRIs of the spine. Our patients had spine MRI and not whole-body MRI that was used in the study by Hillengass et al., which is associated with a

DOI: 10.1038/leu.2014.230

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@article{Kastritis2014ThePI, title={The prognostic importance of the presence of more than one focal lesion in spine MRI of patients with asymptomatic (smoldering) multiple myeloma}, author={Efstathios Kastritis and Lia Angela Moulopoulos and Evangelos Terpos and Vassilios Koutoulidis and M. A. Dimopoulos}, journal={Leukemia}, year={2014}, volume={28}, pages={2402-2403} }