Bone Disease Burden Does Not Seem to Impact Overall Survival in Newly Diagnosed Patients with Multiple Myeloma - a Detailed Imaging Analysis on 119 Patients

Introduction: Whole body low dose computed tomography (WBLDCT) is the cornerstone of detecting myeloma bone disease (MBD) and establishing the diagnosis of symptomatic multiple myeloma (MM). Herein, we evaluated the bone disease burden in patients with newly diagnosed MM using WBLDCT and we explored possible correlations with survival outcomes.

Methods: We consecutively enrolled patients with NDMM who performed baseline WBLDCT assessed at a single referral center according to standard clinical practice. A detailed analysis of bone-related parameters was performed independently by two radiologists with expertise in MM. More specifically, each patient was evaluated for the presence of any osteolytic lesions, the total number and the largest diameter of the lesions, the presence of cortical destruction, the presence of fractures and vertebral compound fractures (VCFs), the presence of appendicular skeleton medullary cavities (ASMC) characterized as fatty, nodular, diffuse or mixed, their density in Hounsfield units and their localization. Each bone (skull, cervical spine, thoracic spine, lumbar spine, sacrum, left and right innominates, left and right ribs, left and right clavicles, left and right scapulae, sternum, left and right femurs, left and right humerus) was assessed separately.

Results: 119 patients (57.5% females) were included, with a median age of 67 years (range 37-81). Patients were assessed per ISS and R-ISS stage as follows: 31 (26.3%) and 20 (16.9%) stage 1, 30 (25.4%) and 71 (60.2%) stage 2, 57 (48.3%) and 27 (22.9) stage 3, respectively. As per R2-ISS they were distributed as follows: 48 (40.7%) low risk, 24 (20.3%) low-intermediate risk, 33 (28.0%) intermediate-high risk and 13 (11.0%) high risk. 73 patients (61.3%) had performance status 0-1, whereas 19 (16.1%) had at least one high-risk cytogenetic abnormality.

The patients received induction treatment as follows: 80 (67%) based on proteasome inhibitors, 14 (12%) based on immunomodulatory drugs, 22 (19%) based on both a PI and an IMiD and 3 (2%) based on anti-CD38 monoclonal antibodies. 31 (26.3%) of the patients underwent autologous stem-cell transplantation. During a median follow-up of 4.2 years (range 0.1-5.4), 79 patients (67.0%) showed disease progression and 63 (54.2%) died. The median progression-free survival (PFS) was 2.19 years (95% CI: 1.61-3.31) and median overall survival (OS) was 6.24 years (95% CI: 4.06-not reached).

Regarding osteolysis assessment, the median (range) number of osteolyses in each bone group were as follows: 2 (0-96) for the spine (cervical spine, thoracic spine, lumbar spine, sacrum), 0 (0-30) for the skull, 0 (0-41) for the shoulder (left and right clavicles, left and right scapulae), 0 (0-28) for the appendices (left and right femurs, left and right humerus) and 0 (0-42) for the ribs (right and left ribs). Regarding the ASMC assessment in the bilateral femurs and humerus, 47 patients (39.5%) showed fatty ASMCs, 39 patients (32.8%) had diffuse ASMCs, 30 patients (25.2%) had nodular ASMCs, whereas 38 patients (31.9%) had mixed ASMCs subtypes.

The 119 patients were stratified according to the presence (n=52) or absence (n=67) of VCFs. When applying the presence or not of VCFs as a single predictor for PFS and OS, the results of Kaplan-Meier survival estimation and Cox proportional hazards regression both showed significantly worse survival if at least one VCF was present. More specifically, the median PFS was 42.7 months for patients without VCFs compared to 19.8 months for patients with at least one VCF (HR 1.69, 95%CI: 1.09 - 2.62, P = 0.02). Similarly, the median OS was prolonged in patients without VCFs compared to those with at least one VCF (HR 1.99, 95%CI: 1.21-3.25, P = 0.006). However, among all the examined imaging variables, no factor or combination factors had independent significance for patient prognosis.

Conclusions:

Although the presence of VCFs at WBCT at diagnosis of MM was correlated with survival outcomes in the univariate analysis, none of the imaging parameters retained statistical significance in the multivariate analysis. Therefore, it seems that the extend of the MBD burden at diagnosis does not impact OS in the era of modern anti-myeloma treatment regimens.

Terpos:GSK: Honoraria, Research Funding; EUSA Pharma: Honoraria, Other: Travel expenses; Janssen: Honoraria, Research Funding; Menarini/Stemline: Honoraria; Amgen: Honoraria, Other: Travel expenses, Research Funding; Pfizer: Honoraria; AstraZeneca: Honoraria, Other: Travel expenses; BMS: Honoraria; Sanofi: Honoraria, Other: Travel expenses, Research Funding; Takeda: Honoraria, Other: Travel expenses, Research Funding; Novartis: Honoraria; Antengene: Honoraria, Research Funding; Swixx: Honoraria. Ntanasis-Stathopoulos:AstraZeneca: Honoraria; Janssen-Cilag: Honoraria; Cellectar Biosciences: Research Funding. Mavropoulos-Papoudas:HeaDs: Current Employment. Gavriatopoulou:Janssen Cilag: Honoraria; Swixx: Honoraria; Takeda: Consultancy, Honoraria; Integris: Honoraria; GSK: Consultancy, Honoraria; Cellectar Biosciences: Research Funding; BMS: Research Funding; AbbVie: Honoraria; Beigene: Research Funding; Amgen: Consultancy; Karyopharm: Consultancy; Genesis Pharma: Honoraria. Fotiou:Sanofi: Honoraria; Janssen: Honoraria. Migkou:Janssen Cilag: Honoraria; GlaxoSmithKline: Honoraria. Kastritis:Genesis Pharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Prothena: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Honoraria. Dimopoulos:Menarini: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Consulting fee; GlaxoSmithKline: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Consulting fee; BeiGene Inc: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Consulting fee; Regeneron: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Consulting fee; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Consulting fee; Swixx: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Consulting fee; AstraZeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen, Abbvie, Takeda, Beigene, BMS, GSK, Janssen, Menarini, Regeneron, Sanofi: Other: Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Consulting fee; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Consulting fee.