The Clinical Characteristics and Epidemiology of Extramedullary Multiple Myeloma over the Past Two Decades

Background

Extramedullary multiple myeloma (EMM) represents a rare and aggressive manifestation of multiple myeloma (MM) in which plasma cells survive outside of the bone marrow microenvironment, arising from a non-medullary site. EMM affects approximately 30% of MM patients and can be present at diagnosis or develop at any timepoint during the disease course [1,2]. Prior studies have demonstrated a higher incidence of high-risk cytogenetics in patients with EMM including gain 1q, translocation (4;14), translocation (14;16) and deletion 17p [3]. There is a paucity of data on clinical characteristics and overall epidemiology of EMM. The purpose of this study is to evaluate the clinical characteristics of patients with EMM over the past 2 decades, and to identify epidemiologic characteristics that may impact overall prognosis.

Methods

A population-based retrospective cohort study of patients with EMM was conducted using the publicly available Surveillance, Epidemiology, and End Results (SEER) database. In addition, 18 registries in the November 2020 submission database were also utilized (http://www.seer.cancer.gov). All patient-specific information within the databases have been de-identified, and therefore IRB approval was not needed to conduct this study. A total of 858 patients diagnosed with EMM, between 2000 and 2017, were ultimately enrolled in our study. We analyzed demographics, clinical characteristics, and overall mortality (OM) as well as cancer-specific mortality (CSM) of EMM. Variables with a p-value < 0.1 in the univariate Cox regression were incorporated into the multivariate Cox model to determine the independent prognostic factors, with a hazard ratio (HR) of greater than 1 representing adverse prognostic factors. All tests were two-sided, with a confidence interval set as 95% and p value <0.05 deemed statistically significant. All statistical tests were performed by using Software STATA 16.1.

Results

From a sample of 858 patients with EMM, male gender (63.25%), age range 60-79 years (51.05%) and non-Hispanic whites (66.78%) were the most represented. Central Nervous System (which includes leptomeningeal, intracranial and intraparenchymal involvement) and vertebral column was the most affected site (33.10%). Multivariate cox proportional hazard regression analyses only revealed higher overall mortality (OM) in age group over 80 years (HR = 9.792, 95% CI 4.403-21.774, p=0) and widowed individuals (HR = 1.609, 95% CI 1.101-2.35, p = 0.014). Multivariate cox proportional hazard regression analyses of cancer specific mortality (CSM) also revealed higher mortality of the same groups. Eyes, mouth, and ENT involvement had the lowest CSM in the multivariate analysis.

Conclusions

EMM is a relatively rare entity that presents in a minority of patients diagnosed with MM [1]. To our knowledge, there is scarcity of data on the clinical characteristics and epidemiology of patients with EMM. This study found that non-Hispanic whites were the most affected population, which contrasts with the overall epidemiology of Multiple Myeloma without extramedullary disease in which the black population is the most affected [4]. Patients were primarily in the 60-79-year age range, and the most commonly affected sites were CNS/vertebral column (33%), bones/soft tissues of the trunk (12.6%) and pelvis/sacrum (11.3%), and eyes/mouth/ears/nose/throat (11.7%). We found that age was the single most important prognostic factor, with older patients having worse outcomes (Table 2). Marital status and tumor location were also found to be independent prognostic factors, with widowed patients having higher mortality rates and patients with EMM affecting eyes/mouth/ears/nose/throat faring better than those with other sites affected (Table 2). We hope that the results of this study will enhance our overall understanding of the clinical presentation of this rare and aggressive manifestation of MM. In better understanding EMM, we hope to inspire larger prospective studies on the management of this subset of patients, which is particularly important in the era of novel agents including immunomodulatory agents, proteasome inhibitors, monoclonal antibodies, and, more recently, the advent of chimeric antigen receptor T-cell therapy (CAR-T) and bispecific agents.

Siegel:GSK: Honoraria, Speakers Bureau; COTA: Current equity holder in private company, Current holder of stock options in a privately-held company; BMS: Honoraria, Speakers Bureau; Takeda: Honoraria; Janssen: Honoraria; Merck: Honoraria; Celularity: Membership on an entity's Board of Directors or advisory committees. Biran:Amgen, Janssen, Karyopharm, Merck, BMS, Sanofi: Consultancy, Research Funding. Parmar:Janssen: Consultancy, Honoraria.