Correlation of Serological and MRI-Based Treatment Response to Systemic Chemotherapy In 100 Patients with Multiple Myeloma

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.