PS1364 EXOSOMAL CARGO IN MONOCLONAL GAMMOPATHIES COMPARED TO HEALTHY DONORS AND ITS POTENTIAL RELATION TO MYELOMA AGGRESSIVENESS
Authors: Ferreira B. , Carneiro E. , Barahona F. , Lucio P. , Neves M. , Costa‐Silva B. , Joao C. 
Published: June 2019

Background:

Multiple myeloma (MM) is characterized by a clonal proliferation of neoplastic plasma cells (PCs) in bone marrow (BM) and the interaction between MM PCs and the BM microenvironment plays a relevant role in its pathogenesis. MM is virtually always preceded by two asymptomatic conditions — first monoclonal gammopathy of undetermined significance (MGUS) and then smoldering multiple myeloma (SMM). SMM is a heterogeneous clinical entity where some patients have an indolent course similar to MGUS, whereas others have a more aggressive course developing clinical symptoms and end‐organ damage in a few years from diagnosis. Currently there is no single pathological or molecular feature that can be used to distinguish SMM patient's PC from overt myeloma's PC. Exosomes (EXO) are extra vesicular particles released in circulation by cells. Exosomal cargo has recently been studied in the cellular cross‐talk between MM and the BM microenvironment and have the potential to be used as new biomarkers of disease aggressiveness as liquid biopsies.

Aims:

1. To collect and analyze differences between circulating serum EXO in a cohort of MM, SMM and MGUS patients versus healthy donors (HD); 2. to analyze the potential relation between Exo cargo and disease aggressiveness.

Methods:

EXO were isolated from patient's plasma samples by sequential ultracentrifugation. EXO number and size was analyzed by NanoSight and protein quantity (EXO cargo) was determined by the ratio between quantity of proteins and number of exosomes. Comparisons among groups (MM = 15, SMM = 7, MGUS = 7) and HD (n = 6) were made regarding EXO size and Exo cargo.

Results:

Clinically, the median age of MM patients was 78yo vs MGUS 72 yo vs HD 75 yo. Most MM patients (60%, n = 9) were previously treated (33% (n = 5) 1line; 20% (n = 3) 2 lines and 7% (n = 1) 3 lines) vs 40% (n = 6) not treated (0 lines). R‐ISS I (n = 7); II (n = 1) and III (n = 7). In our cohort, 86% of SMM (n = 6) patientswere low risk according to Mayo Clinic Score, and 1 (14%) patient, with high risk score, progressed to MM in less than 2 years; 57% of MGUS (n = 4) patients were low risk and 43% (n = 3) were low intermediate risk according to Mayo Clinic Score. In all groups EXO were isolated, with no significant differences in median particles size (MM 120 (99.5–138.5) nm; SMM 116.4 (108.6–143.4) nm vs MGUS 131.0 (117.9–142.0) and HD 126.6 (110.8–150.1) nm. MM patients revealed 5 and 3xtimes higher circulating EXOcargo (ug/EXO) when compared to MGUS and SMM patients, respectively (p < 0.05, n = 15 MM; n = 7 MGUS and SMM n = 7); MM median 2.34 (1.08–6.5) ug/EXO vs MGUS median 0.42 (0.28–1.1) and SMM median 0.87 (0.61–1) ug/EXO. There were no differences regarding the EXOcargo between SMM and MGUS compared to HD (n = 6, HD median 0.88 (0.57–1.83) ug/EXO).

Summary/Conclusion:

Although preliminary, these data group together new results of Exo cargo in SMM and MGUS patients. Both MGUS and SMM presented with EXO cargo similar to HD and significantly lower than the EXO cargo found in MM patients. Interestedly, the majority of MGUS and SMM patients included in our cohort were low risk patients and this is probably reflected in their similar EXO to HD. The proteins and mRNA included in these EXOs are being analyzed and will be tested as potential biomarkers of disease aggressiveness.