**2. Diagnosis, staging, genetics and risk stratification**

The diagnostic criteria for MM are: (1) clonal BM plasma cells ≥10% or biopsy-proven bony or extramedullary plasmacytoma and (2) at least one of the following: (a) evidence of end-organ damage such as anemia, lytic bone lesions, hypercalcemia and renal insufficiency, (b) clonal BM plasma cells ≥60%, (c) involved:uninvolved serum free light chain ratio ≥100 and (d) at least two focal lesions on magnetic resonance imaging [8, 10–15].

MM is usually classified into three stages: (1) stage I; all the following: serum albumin ≥3.5 g/ dL, serum beta 2 microglobulin (B2M) < 3.5 mg/L, normal serum lactic dehydrogenase (LDH) and no high-risk (HR) cytogenetics; (2) stage II: not fitting stages I and III with serum B2M: 3.5–5.5 mg/L, and (3) stage III; all the following: serum B2M > 3.5 mg/L and HR cytogenetics or elevated serum LDH level [8, 13].

The following cytogenetic abnormalities have been reported in patients with MM: trisomies; monosomies; 17 p deletion; amp (1q20); t(14,16); t(14,20); t(4,14); t(6,14) and t(11,14) [8, 13, 16]. Also, the following molecular mutations have been reported in MM patients: NRAS, KRAS, TP53, BRAF, CCND1, FAM46C, MYC, XBP1, EZH2 and CHST15 [17–21]. Recently, the following laboratory techniques have been utilized in the diagnosis and follow-up of patients with MM: (1) next-generation sequencing (NGS), (2) genomic and epigenetic studies, (3) micro-RNA and (4) minimal residual disease (MRD) evaluation by flow cytometry, polymerase chain reaction, and NGS [17–22]. Mass accumulation rate will be used in the near future for susceptibility of human MM cell lines to standard-of-care therapies [23].

The HR features in MM include: (1) cytogenetic and molecular abnormalities that include: hypodiploid, 17 p deletion, t(4,14), t(14,16), t(14,20) and EZH2; (2) international scoring system stage II or III; (3) presence of comorbid medical conditions that limit therapy; (4) extramedullary disease (EMD) and (5) renal failure, high serum LDH level and plasma cell leukemia [13, 16, 21, 24, 25]. MM patients are stratified into three risk groups based on their cytogenetic profiles as follows: (1) HR that includes 17 p deletion, t(14,16) or t(14,20); (2) intermediate risk that includes: t(4,14) and amp (1q20)/gain (1q) and (3) standard risk that includes: trisomies, t(11,14) and t(6,14) [8, 13, 16]. Additional poor prognostic features include: age ≥60 years and refractory and/or relapsed MM (R/R-MM) [26].
