Whole-Body Reduced-Dose CT As Primary Staging and during Follow-up in First-Line Treatment of Transplant-Eligible Multiple Myeloma Patients: Results of the German GMMG-MM5 Trial
Authors: Weisel Katja , Horger Marius , Goldschmidt Hartmut , Kanz Lothar , Delorme Stefan , Hillengass Jens 
Published: October 2019

Abstract
Background: Detection of myeloma bone disease defined still relies on the use of projection radiography (PR). The limitations of plain radiographs are well known. Reduced-dose whole-body computed tomography (wbrd-CT) is a broadly available, highly sensitive and patient-friendly method for precise detection of myeloma bone disease. The GMMG-MM5 phase III trial included 604 primary diagnosed multiple myeloma (MM) patients up to the age of 70 years who received a bortezomib based three-drug combination induction regimen followed by stem cell mobilization and 1-2 cycles of high-dose melphalan and autologous stem cell transplantation followed by a lenalidomide consolidation and maintenance. In this trial, wbrd-CT was preferably used in all trial centers for myeloma staging and, as clinically indicated, during follow-up. To the best of our knowledge, so far there are no systematic data on the radiographic disease course of myeloma bone disease after bortezomib-based induction and high-dose melphalan treatment. Here, we present data of 2 GMMG centers for the use of wbrd-CT for initial staging and during follow-up.
Methods: In 2 german centers a total of 231 patients were included into the GMMG-MM5 trial. In 201 patients, wbrd-CT for initial myeloma staging was available, currently 44 patients were evaluated. Wbrd-CT were performed unenhanced (no oral or IV contrast agent) on a MDCT. In all patients, the scan length was adapted (approximately 150cm), from the roof of the skull down to the knees (dependent on patient’s height, mostly down to the proximal tibialmetaphyses). Patients were positioned supine, head first, with the arms stretched in elevation and abduction over the head or crossed ventral of the abdomen, in order to be able to analyze bone. Imaging data was reviewed by 2 independent radiologists. All patients received bisphosphonates as supportive treatment.
Results : So far, 44 patients with wbrd-CT at baseline and 41/44 at follow-up were analyzed. At baseline, 36/44 patients showed osteolytic destruction (>20 lesions [n=20]; <20 [n=11]; <4 [n=4], 1 [n=1]), 5 showed osteopenia, 8 bone plasmocytoma. Follow-up investigations were performed after high-dose melphalan treatment at 6 months after initial staging as well was at 12 and 24 months in a smaller patient cohort. During follow-up, 39 patients showed no new or progressive lesions whereas 2 patients showed progressive bone destruction. 5 patients showed resclerosis of osteolysis after 6 months, another 2 patients experienced sclerosis 1 year after treatment defined by increased attenuation of bone inside or at the margin of pre-existent lesions or inside medullary lesions or even shrinkage or disappearance of osteolyses. 1 patient showed reduced number of osteolyses at 3rdFU (18 months). Attenuation of medullary lesions (BMA) declined at FU except in 2 patients. Even in patients showing PD at 6 months, BMA slightly decreased. 23/41patients showed complete remission of medullary infiltration defined by a density of existing lesions of <20 Hounsfield Units HU) at 6 months. 34/41 patients showed complete remission at 12 months. 4/7 patients showed remission of extramedullary disease at 6 months and 6/7 at 1 year after treatment. 3 patients showed progressive disease at 1st FU (6 months), 1 at 2nd FU (12 months) and another 3 patients at 4thFU (24 months). Analysis of the total patient cohort will be presented at the meeting.
Conclusions : Wbrd-CT is a broad available and highly sensitive radiographic method for detection of myeloma bone disease. Here, we show to the best of our knowledge for the first time a prospective evaluation of this method in a phase III multicenter trial for first-line treatment in transplant-eligible MM patients. It is shown, that wbrd-CT allows documentation of myeloma bone disease. Furthermore, medullary and extramedullary lesions are detected. During follow-up we demonstrate, that a substantial proportion of 17% of patients show resclerosis of existing lesions. Follow-up investigations of medullary lesions allow extended response assessment. In our view, wbrd-CT should be the new standard of care for detection of myeloma bone disease even in a multicenter trial setting. Effective bortezomib-based induction treatment may result in resclerosis in a substantial proportion of patients.

Disclosures
Weisel: Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Onyx: Consultancy, Honoraria; Noxxon: Consultancy; Bristol Myers Squibb: Consultancy. Off Label Use: Lenalidomide is used in an off-label setting in consolidation and maintenance in the GMMG-MM5 trial. Goldschmidt:Onyx: Consultancy, Speakers Bureau; Chugai: Research Funding, Speakers Bureau; Novartis: Honoraria, Research Funding, Speakers Bureau; Celgene: Honoraria, Research Funding, Speakers Bureau; Polyphor: Research Funding; Janssen-Cilag: Honoraria, Research Funding, Speakers Bureau; Millenium: Consultancy, Speakers Bureau. Hillengass:Medtronic: Honoraria; Janssen: Honoraria; Celgene: Honoraria.