Cytogenetic Abnormalities and Appearance of Multiple Myeloma in Whole Body-MRI.
Authors: Hillengass Jens , Fechtner Kerstin , Jauch Anna , Baeuerle Tobias , Hielscher Thomas , Heiss Christiane , Ayyaz Sofia , Hose Dirk , Weber Marc-André , Goldschmidt Hartmut , Neben Kai 
Published: October 2019

Abstract
Abstract 4868

Introduction
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.

Results
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.

Conclusion
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.

Disclosures
No relevant conflicts of interest to declare.