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4468 Findings of Whole Body Computed Tomography Compared to Conventional Skeletal Survey in Patients with Monoclonal Plasma Cell Disorders – a Study of the International Myeloma Working GroupClinically Relevant Abstract

Myeloma: Pathophysiology and Pre-Clinical Studies, excluding Therapy
Program: Oral and Poster Abstracts
Session: 652. Myeloma: Pathophysiology and Pre-Clinical Studies, excluding Therapy: Poster III
Monday, December 5, 2016, 6:00 PM-8:00 PM
Hall GH (San Diego Convention Center)

Jens Hillengass, MD1,2, Lia A. Moulopoulos, MD3*, Stefan Delorme, MD2*, Vassilis Koutoulidis, MD3*, Thomas Hielscher4*, Jessica Engelhart2*, Matthew T. Drake, MD, PhD5, S. Vincent Rajkumar, MD5, Brian Oestergaard, MD6*, Niels Abildgaard, MD, Professor6, Maja Hinge, MD7*, Torben Plesner, Professor8,9, Yasuhito Suehara, MD10*, Kosei Matsue, MD, PhD11, Jo Caers12*, Nadia Withofs, MD13*, Meletios Dimopoulos14, Hartmut Goldschmidt, MD15,16, Suzanne Lentzsch, MD, PhD17, Brian G Durie, MD18 and Evangelos Terpos, MD, PhD19

1Dept. Med. V, University Hospital Heidelberg, Heidelberg, Germany
2Department of Radiology, German Cancer Research Center, Heidelberg, Germany
3First Department of Radiology, National and Kapodistrian University of Athens, School of Medicine, Areteion Hospital, Athens, Greece
4Department of Biostatistics, German Cancer Research Center, Heidelberg, Germany
5Mayo Clinic, Rochester, MN
6Department of Hematology, Odense University Hospital, (University of Southern Denmark), Odense, Denmark
7Department of Haematology, Odense University Hospital, (University of Southern Denmark), Odense, Denmark
8Vejle Hospital, Vejle, Denmark
9Department of Hematology, Vejle Hospital and University of Southern Denmark, Vejle, Denmark
10Tsukuba University Medical School, Tsukuba, Japan
11Kameda Medical Center, Kamogawa, Japan
12Department of Hematology, CHU de Liège, Liège, Belgium
13Department of Nuclear Medicine, CHU de Liège, Liège, Belgium
14National and Kapodistrian University of Athens, School of Medicine, Therapeutics, Athens, Greece
15Department of Hematology and Oncology, University Hospital Heidelberg, Heidelberg, Germany
16National Center for Tumor Diseases, Heidelberg University Hospital, Heidelberg, Germany
17Division of Hematology/ Oncology, Columbia University Medical Center, New York, NY
18Cedars-Sinai Outpatient Cancer Center, Los Angeles, CA
19Department of Clinical Therapeutics, National and Kapodistrian University of Athens, School of Medicine, Alexandra General Hospital, Athens, Greece

Introduction: For decades conventional skeletal survey (CSS) has been the standard imaging technique for the detection of bone impairment caused by Multiple Myeloma (MM). The development of cross-sectional imaging techniques like Whole Body Computed Tomography (WBCT) with or without Positron Emission Tomography (PET/PET-CT) and magnetic resonance imaging (MRI) led to the use of these techniques in several centers worldwide and to the implementation of their findings into the revised diagnostic criteria of MM. The aim of the current multicenter study was to compare sensitivity and prognostic significance of WBCT and CSS in patients with monoclonal plasma disorders.

Methods: For the current retrospective analysis 308 patients with different stages of monoclonal plasma cell disorders from 8 centers were included. Compact discs with pseudonymized imaging data of WBCT and CSS were sent to the organizing center and uploaded to the picture archiving and communication system. In addition, questionnaires were completed by each center to collect clinical data of the patients. Image analysis was performed in consensus reading by three experienced radiologists (LAM, SD, VK) blinded to the clinical data of the patients. Osteolytic lesions in 19 pre-specified anatomic regions were characterized as “definitely present”, “probably present”, “probably absent” and “definitely absent”. For the analysis only “definitely present” and “probably present” entries were counted as myeloma lesions. To define symptomatic or active versus smoldering myeloma based on the presence of bone lesions, findings of CSS were used to simulate the situation before the introduction of WBCT. For comparison of WBCT and CSS only those anatomic regions having valid measurements from both methods performed within 30 days without treatment in the meantime were considered. WBCT and CSS were tested for differences in detection sensitivity with the exact McNemar test.

Results: Of 308 submitted datasets; 160 patients were without prior treatment and 56 of them had smoldering myeloma. Of 160 patients 80 (50%) had no osteolytic lesions on either CSS or WBCT and 33 (20.6%) showed osteolyses on both techniques. In 9 patients (5.6%) osteolyses were found on CSS but not in WBCT while 38 patients (23.8%) were positive on CT alone. Of note is that for some CT-scans, the upper extremities were not evaluable due to positioning during the examination. Odds ratio for osteolyses on WBCT compared to CSS was 4.22 (P < 0.0001). The regions where WBCT was most significantly superior in detecting osteolyses were the iliac bone, thoracic and lumbar spine as well as the ribs. CSS compared to WBCT revealed osteolyses in more patients only in the proximal extremities: for left humerus 10 (6.5%) versus 3 (1.9%), right humerus 12 (7.7%) versus 4 (2.6%), left femur 11 (7.1%) versus 7 (4.5%) and right femur 10 (6.5%) versus 8 (5.2%) respectively. Of 157 evaluable patients 63 (40.1%) showed osteoporosis (defined by radiological criteria) on both techniques while 29 (18.5%) had osteoporosis on WBCT only and 10 (6.4%) on CSS only (OR 2.90, P = 0.003). In the 56 patients with smoldering myeloma, with bone disease being defined according to the findings of CSS 12 (21.4%), were positive for osteolyses on WBCT (P = 0.0005).

Conclusion: WBCT shows significantly more sites of bone destruction compared to conventional X-ray imaging particularly in skeletal regions composed primarily of trabecular bone while CSS shows more osteolyses in the appendicular skeleton – in part due to a limited field of view. More than 20% of patients with smoldering myeloma based on CSS have active disease that needs treatment based on WBCT. Therefore, WBCT is the current standard for the detection of osteolytic lesions in myeloma. The prognostic significance of WBCT and CSS findings for survival and correlation with clinical parameters will be reported at the meeting.

Disclosures: Hillengass: Celgene: Honoraria; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria; Novartis: Research Funding; Amgen: Consultancy, Honoraria; Sanofi: Research Funding. Plesner: Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding. Dimopoulos: Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Onyx Pharmaceuticals: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Genesis: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Goldschmidt: Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Chugai: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Millennium: Membership on an entity's Board of Directors or advisory committees, Research Funding; Onyx: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees. Lentzsch: Celgene: Consultancy, Honoraria; BMS: Consultancy. Terpos: Bristol-Myers Squibb: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Novartis: Honoraria; Takeda: Consultancy, Honoraria; Genesis: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Celgene: Honoraria.

*signifies non-member of ASH