Clinical and Radiographic Course of Bone Disease in Relapsed Multiple Myeloma in the Era of Novel Agents: Occurrence, Definition and Impact of Resclerosis Documented by Whole-Body Low-Dose Multidetector Computed Tomography
Authors: Oehrlein Katharina , Horger Marius , Schmidt Anja , Zago Manola , Schulze Maximilian , Kanz Lothar , Weisel Katja C 
Published: October 2019

Abstract
Abstract 3963
Despite the important progress obtained by the introduction of novel agents in the treatment of multiple myeloma (MM), osseous complications caused by the disease remain an important cause of morbidity impacting negatively on the patients′ quality of life. Although conventional radiographic assessments can detect the extent of bone disease, they are not able to assess the potential of new agents to induce resclerosis – as an indicator of bone remodelling - of bone lesions. Assessment by multidetector computed tomography (MDCT) not only offers the highest sensitivity for detection of osteolytic lesions while minimizing radiation exposure, but also allows precise estimation of instability and fracture risk. Most importantly, this technique documents the extent of treatment-induced resclerosis of MM bone disease. Increased stability of osseous lesions is of high impact for quality of life in the individual patient (pt). So far, there are no systematic data assessing the impact of novel agents on the pattern of resclerosis in MM. We therefore analysed 115 pt with newly diagnosed (n=25) and relapsed or refractory (rr) (n=90) MM disease who were treated at our institution between 2004 and 2011 with bortezomib (bort) and/or lenalidomide (len) (49 bort only, 30 bort and subsequent len, 36 len only). MDCT was employed for assessment of osseous lesions according to clinical symptoms or disease course following institutional guidelines. Also, bisphosphonates were applied according to institutional guidelines. Sclerosis was defined as increase in CT-attenuation of bone and was expressed in Hounsfield units (HU). Sclerotic changes detected by MDCT were documented according to localization, number, character (disseminated vs. focal) and site (inside medullary or extramedullary lesions) or described as sclerotic rim surrounding known osteolyses.
Median pt age was 63 years, median number of treatment lines were 1 in the bort and 2 in the len group. Resclerosis was documented in 14 pts (17.7%) under bort and in 7 (10.6%) pts under len treatment. Sclerotic changes occurred as focal sclerosis of osteolyses (n=16), focal sclerosis of medullary lesions (n=4) or diffuse sclerosis of the bone (n=4) with combinations of various patterns being detected in individual pt. One pt responding to bort and, in subsequent relapse, also to len showed different patterns of resclerosis under each treatment. Pts experiencing sclerotic changes under bort, in 7 cases had a PR, 2 VGPRs, 1 CR and 4 had SD as best treatment response. All Pts with sclerotic changes under len showed at least a PR with 1 pt achieving CR. In 1 pt response was not evaluable due to oligosecretoric disease. Median numbers of pretreatments were 1 (range 0–5) in pts with sclerotic changes in the bort and 2 (range 0–2) in the len group. Sclerotic changes persisted indepently of the subsequent disease course. Individual pt courses will be demonstrated.
Resclerosis of bone lesions is a new phenomenon in MM pts which occurs under bort and len treatment. To the best of our knowledge this is the first systematic evaluation of the pattern of resclerosis observed under the respective treatments. We provide first evidence that sclerotic changes occur in a small, but marked proportion of pts with a high variety regarding the observed pattern (diffuse versus focal) and localisation (osseous or medullary). Whereas under len treatment resclerosis was solely detected in pts with at least PR, sclerotic changes under bort treatment even occurred when myeloma response was suboptimal. This might be explained by different effects of both drugs on the bone marrow microenvironment. Prospective evaluation of this phenomenon and systematic correlation to genomic profile is warranted.

Disclosures:
Weisel: Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees.