Focal Lesion (FL) Identification by MRI and Metastatic Bone Survey (MBS) in Multiple Myeloma (MM): Laboratory Correlates and Prognostic Implications for 611 Patients Receiving Total Therapy 2 (TT2).

Abstract

Background: The Durie-Salmon staging system utilizes both laboratory features and information on MBS-FL. We hypothesized that, by detecting FL in the bone marrow prior to MBS-recognizable bone destruction, MRI would provide a biologically and clinically more relevant feature of FL-type MM (Tian et al, NEJM 2003).Patients and Methods: As part of a tandem transplant trial, TT2, MBS, MRI, clinical workup and cytogenetics were performed on 611 cases.Results: In a comparison of all areas imaged by both techniques, at least one FL was detected in 451 (74%) on MRI and 344 (56%) on MBS; 128 (21%) had no FL by either technique while 312 (51%) showed FL on both MBS and MRI. Importantly, of 267 patients without FL on MBS, 139 (52%) had FL on MRI; conversely, among 160 without FL on MRI, 32 (20%) had FL on MBS examination. The mean FL number among those with FL was 13 in case of MRI and 8 with MBS. Significantly higher proportions of patients had FL on MRI than MBS in spine (78% vs. 16% p<0.001), pelvis (64% vs. 28%, p<0.001) and sternum (24% vs. 3%, p<0.001). Higher FL number on both MRI and MBS and heterogeneity of the diffuse marrow signal on MRI STIR (indicating micro-nodular disease), cytogenetic abnormalities (CA), elevated serum levels of beta-2-microglobulin (B2M), C-reactive protein (CRP) and lactate dehydrogenase (LDH), in case of hypo-albuminemia and advanced age, were prognostically negative. On multivariate analysis (MVA), MRI- but not MBS-defined FL number was an independent adverse baseline feature for overall survival (HR=1.73; p<.001), independent of CA (HR=2.11; p<.001) and elevations of LDH (HR=1.56; p=.006) and B2M levels (HR=1.43; p=.026). Clinical complete response (CCR) (MVA HR=0.60; p=0.007) and MRI-CR (univariately: HR, 0.58; p=0.004) were favorable features when examined as time-dependent variables along with baseline features. Higher MRI-FL number (>7) was significantly associated with higher serum levels of LDH, CRP and creatinine as well as with hypo-albuminemia, whereas no correlations were noted with levels of B2M, bone marrow plasmacytosis, hemoglobin, CA, age, gender, race and Ig isotype.Conclusion: MRI examination in MM is justified:as an imaging tool that permits detection of FL long before osteolytic disease is recognized on MBS,as an independent staging tool with prognostic implications (that should replace MBS used in the Durie-Salmon staging system) after accounting for the presence of CA, LDH and B2M;as a means of documenting a superior state of CR (MRI-CR) conferring survival advantage, in patients with a high focal lesion number at baseline; and, not addressed here,as a tool for detecting and staging non-secretory and macro-focal MM, the latter often having minimal or no involvement on random bone marrow examination. [Display omitted]