Geographical Variation Shows Differences in Disease Characteristics Among Patients with Multiple Myeloma.
Authors: Ailawadhi Sikander , Keng Michael , Mohrbacher Ann , Thara Eddie , Yang Dongyun , Sher Taimur , Patel Mehul P , Miller Kena C , Groshen Susan , Chanan-Khan Asher A. 
Published: October 2019

Abstract
Abstract 4895

Background
Multiple myeloma (MM) remains an incurable cancer. Several biological and environmental factors have been considered to contribute to its pathogenesis, but so far no clear etiology is known. It remains undetermined if geographical differences and variability in environmental factors influences biological behavior and clinical presentation of MM patients. In depth research into the regional and demographic variation of these characteristics has not yet been done. To evaluate the impact of environmental influences we compared MM disease characteristics in two distinct geographical regions.

Methods
Patients with plasma cell disorders seen in the malignant hematology clinics of the University of Southern California (USC), Los Angeles, CA and the Multiple Myeloma Program Clinic at the Roswell Park Cancer Institute (RPCI), Buffalo, NY were included in this analysis. Demographic and disease-related clinical characteristics at the time of diagnosis of active MM were evaluated. Chi-square test or Mann-Whitney U test were used where appropriate. A 0.05 nominal significance level was used in all hypothesis testing.

Results
One hundred and sixty patients at USC and 170 patients at RPCI were studied. Among these, 140 and 144 had active MM at the time of diagnosis, respectively. The median age at diagnosis was 58 years (range 20-85) and 60 years (range 35-83), and males represented 48% and 52 % of the patients, respectively in the two geographic locations. Predominant patient race was Hispanic at USC (54%) and Caucasian at RPCI (92%). Advanced stage disease (>stage 1) was present in 87% and 85% patients, respectively as per the Durie Salmon (DS) staging and 53% and 48%, respectively as per the International Staging System (ISS). IgG MM was the most common subtype in both locations, but there were a higher number of patients on the West coast with LCO disease (22% vs. 10%). Lytic lesions were noted at the time of diagnosis in 59% of the patients at USC and 78% of the patients at RPCI while non-secretory MM was noted in 9% and 10% of the patients, respectively. There was a statistically significant difference between the patient populations in the two geographical regions with respect to median age at diagnosis (p=0.048), patient race (p<0.001), disease subtype (p=0.018), and presence of lytic bone disease at diagnosis (p<0.001). The difference in median age at diagnosis remained statistically significant even when patients were divided into age cohorts of <50 yrs, <60 yrs, <70 yrs and ≥70 yrs (p=0.03). There was no statistically significant difference between the two groups of patients for gender (p=0.48), DS stage (p=0.22), renal dysfunction (p=0.77), ISS stage (p=0.62), light chain subtype (p=0.72), or secretor status (p=0.75). To ensure that these variations were not just due to ethnic differences, the Caucasian population at USC (n=30) was compared with the Caucasian population at RPCI (n=133). Disease subtype and presence of lytic bone lesions were still significantly different between these groups (p=0.04, and p=0.02, respectively).

Conclusions
Despite widespread heterogeneity amongst MM patients, variations in disease characteristics amongst geographically distinct regions have not been studied systematically. Our investigation represents the first attempt to compare patient characteristics from the West and East coasts of USA. We observe several demographic and clinical characteristics that were significantly different between the two populations that could not be explained based on ethnic influences of the study population. These differences in clinical characteristics may represent undefined environmental influences that are unique to geographic location of the patient(s) and can potentially influence disease biology. Our pilot observation will need validation in a larger patient population to better understand the influences mediated by environmental factors and geographic diversity on clinical and biological behavior of the disease.

Disclosures
No relevant conflicts of interest to declare.