Multiple myeloma (MM) is a malignant clonal disease of plasma cells that accounts for approximately 10% of hematologic malignancies. In the United States, the annual incidence rate is about 4.3 /100,000, with an estimated 20,580 new cases and 10,580 deaths in 2009 [1], and the number of MM patients in China is also increasing year by year. In recent years, the 5-year survival rate of multiple myeloma has risen from 25% in 1975 to 34% in 2003, with new improvements in the last 5 years, attributed to the application of newer and more effective treatments [2], and new understanding of the bone marrow microenvironment has provided the basis for the development of new therapeutic agents. Studies in cytogenetics and molecular biology have revealed that multiple myeloma is a heterogeneous disease and provide strong evidence for assessing prognosis, and that patient treatment must be further refined in order to improve outcomes. Targeted MM therapies (TMTs) for MM are treatments that target the growth and survival of MM cells in the bone marrow microenvironment [3]. The treatment process should target both MM cells (kill tumor cells, inhibit their growth, and induce apoptosis) and take into full consideration the bone marrow microenvironment where tumor cells grow and survive, which are necessary for the survival of MM cells. Through drug therapy, we can change the microenvironment and the way of contact between tumor cells and microenvironment, so that myeloma cells cannot survive in the bone marrow and achieve the purpose of treating MM. New drugs for target site therapy have been widely used in the clinic, including: thalidomide (Thalidomide) and its analog Lenalidomide (Lenalidomide), proteasome inhibitor bortezomib (Bortezomib), etc. This has led to breakthroughs in the treatment of MM, significantly improving the remission rate, remission degree and remission duration of MM patients, and prolonged survival. The response of different patients to treatment regimens varies greatly, which is determined by their biological characteristics (including genetic characteristics). The International MM Study Group defines about one-quarter of patients with median survival less than 2 years as high-risk (High Risk) MM and the rest as standard-risk (Standard Risk) MM, and correctly identifying high-risk patients who die early and developing Therefore, it is extremely important to correctly assess the prognosis of MM and develop a reasonable treatment plan according to different risk levels. The National Comprehensive Cancer Collaborative Network (NCCN) is expected to recommend the International Staging Criteria (ISS) proposed by Greipp et al[4] as an indicator for prognosis assessment in the second edition of the treatment guidelines in 2010. This is staging based on serum albumin and β2-microglobulin levels, and a multivariate analysis of more than 11,000 MM patients worldwide confirmed that ISS staging is a more accurate and simple staging system, with a median survival of 62 months for stage I patients, 44 months for stage II, and 29 months for stage III. To investigate the effect of age on ISS staging, patients were divided into two groups for a comparative study using a cut-off age of 65 years, and it was found that ISS staging remained applicable and was not influenced by age. ISS staging provides an accurate prognostic analysis for patients with MM, whether they receive high-dose chemotherapy combined with hematopoietic stem cell transplantation or patients treated with conventional doses of chemotherapy, and is one of the bases for risk-stratified treatment. In evaluating the prognosis of MM patients, a more comprehensive differentiation has been proposed, using serum albumin, β2-microglobulin, and plasma cell count in peripheral blood to evaluate tumor load, and it has been shown [5] that the number of plasma cells expressing CD38+CD45- per 50,000 circulating mononuclear cells is an independent prognostic factor, whereby staging MM patients with a median survival ranging from 13 months at high risk to 79 months at low risk, while an elevated plasma cell marker index PCLI and an increased proportion of Ki67-positive cells (cells in the proliferative cycle) both suggest a poor prognosis. Multiple myeloma is a heterogeneous disease, and alterations at the chromosomal gene level play an important role in disease onset, progression, and prognosis [6], and cytogenetic abnormalities detected by conventional karyotyping and fluorescence in situ hybridization (FISH) analysis in MM patients undergoing either conventional chemotherapy or hematopoietic stem cell transplantation have a direct impact on prognosis. Konigsberg et al. demonstrated that in MM patients treated with a multi-drug combination regimen based primarily on Marfalan, chromosome 13q14 and 17p13 deletions responded poorly to induction therapy and had a shorter median overall survival (OS) than other patients, while patients with chromosome 11q abnormalities had an even shorter median OS. Another study found that MM patients treated with the M2 regimen (vincristine, capsaicin, marfalan, cyclophosphamide and prednisone) had a median OS of 26 months for patients with t(4:14) and 45 months for controls, 23 months for MM patients with -17p13 and 35 months for patients with -13p14 [7], according to which it has been proposed that for MM cytogenetic different should be treated with risk stratification of patients. Fluorescence in situ hybridization (FISH) allows the detection of genetic alterations specific to interphase cytokinesis, targeting probes 17P (P53), t(11:14) (IgH,cyclin D1), t(4:14) (IgH,FGFR3) and 13q14 (Rb-1) commonly used as indicators for diagnosis and risk stratification therapy. Numerous trials have confirmed that FISH detection of del 17p , t(4:14), t(14:16) and del13q34 suggests short overall survival, acquisition of 1q with deletion of 1p suggests poor prognosis, while t(11:14) is associated with good prognosis [8]. Based on genetic characteristics, combined with the unique clinicopathological features and response of patients to treatment and different prognosis, MM can be clearly classified into two subtypes: hyperdiploid MM with low-frequency IgH gene translocations (H-MM) and non-hyperdiploid MM with high-frequency IgH gene translocations (NH-MM). Combined with chromosomal concomitant translocations, NH-MM is further classified as t(11:14)(q13 : q32 ), t(4:14)(p16 :q32), t(14:16)(q32:q23) and 17p13 deletion types, and such patients are of high risk genetic classification. In addition, patients with chromosome 13 deletion and high proliferation rate (PCLI > 3%) have poor prognosis, and this type of high-risk MM accounts for about 25% of patients, while other patients belong to standard-risk MM patients, accounting for about 75% of patients with common chromosomal abnormalities such as t(11:14), t(6:14), etc. For standard-risk patients, high-dose chemotherapy combined with hematopoietic stem cell transplantation is a good treatment [9], while for high-risk patients, early application of new drugs such as bortezomib for target site therapy is important. Most scholars believe that MM patients with chromosome 13 deletion often predict a poor prognosis, and clinical trials have confirmed that bortezomib can effectively treat relapsed/refractory MM with chromosome 13 deletion with the same efficacy as controls, and MM with chromosome 13 deletion has a short survival when treated with drugs such as dexamethasone, while the addition of bortezomib can overcome the MM patients with chromosome 13 deletion because of the The molecular mechanism of the poor prognosis due to chromosome 13 deletion may be the retinoblastoma (PRb) suppressor gene. The PRb gene is mutated due to uncontrolled transition from G1 to S phase of the cell, resulting in cell cycle dysregulation. Proteasome inhibitors lead to the accumulation of CDK inhibitory proteins P21 and P27, which hinder the cell cycle transition from G1 to S phase, thus eliminating the effects caused by chromosome 13 deletion, and because of this, Mateos et al. combined bortezomib with MP (VMP) to treat 60 patients with MM over 65 years of age [11], showing an overall remission rate of 89% with VMP, with 32% of patients achieved CR and another 11% nCR. the VMP regimen had an incident-free survival (EFS) and overall survival (OS) of 83% and 90% at 16 months, respectively, compared to 51% and 62% in the control MP regimen group. Further studies found that the addition of bortezomib to the MP regimen produced high remission rates with or without FISH-determined chromosome 13 deletions and IgH translocations, and a large national standard phase III study (VISTA trial) was completed with a total of 151 centers in 22 countries worldwide enrolling A total of 682 patients with primary MM were treated with VMP versus MP regimens, with an overall response rate of 71% ORR and 30% CR in the VMP regimen, compared with 35% ORR and 4% CR in the MP regimen. A French study showed that the application of high-dose chemotherapy including a bortezomib regimen combined with hematopoietic cell transplantation resulted in higher-quality remissions and a better prognosis. Patients with t(4:14) often have a high level of the epithelial fibroblast growth factor receptor FGFR-3, and reports have shown that such patients have progression at an average of 8 months after hematopoietic stem cell transplantation [12], suggesting that the non-transplant route is more suitable for such patients, and newly developed drugs specifically targeting the FGFR-3 tyrosine kinase have been shown to have high activity in clinical trials and are starting to enter clinical use . MM patients with t(4:14) have a poor prognosis even without FGFR-3 expression, and the MP regimen combined with FGFR-3 inhibitor therapy is an effective and reasonable approach to best target therapy for such patients, with significant efficacy in preliminary clinical applications. Chromosomal abnormalities in multiple myeloma occur throughout the course of the disease, and rearrangements of the IgH gene occur in almost all patients. In order to treat MM more effectively, it is first necessary to assess the prognosis and risk level of patients based on multiple methods including chromosomes, and use more reasonable protocols to treat different patients. Studies have shown that the targeted therapeutic drug thalidomide and its analogue lenalidomide can directly induce apoptosis, prevent the adhesion of myeloma cells to bone marrow stromal cells, inhibit the secretion of adverse cytokines such as IL-6, and have significant anti-angiogenic effects. Palumbo and colleagues reported a randomized trial of 255 primary MM patients (including high-risk patients) treated with MPT (marfalan and prednisone, thalidomide) or MP (marfalan and prednisone) regimens [13], with an overall response rate of 76% for MPT and 47.6% for MP. 47.6%; complete remission rate: MPT was 15.5% versus 2.4% for MP. In addition, the 2-year event-free survival rate was 54% for MPT versus 27% for MP, and the anti-MM effect of lenalidomide was stronger. Recent studies have shown that bortezomib significantly improves the poor prognosis associated with t(4:14) and chromosome 13 deletions. Therefore, early application of targeted therapeutic agents should be used for adequate treatment of high-risk MM whether or not hematopoietic stem cell transplantation is prepared, and long-term maintenance with drugs such as thalidomide should be added after achieving efficacy, and hematopoietic stem cell transplantation is the best choice for treatment of patients with standard-risk MM. Chen Shilun, 100043 Beijing Medical Research Center for Multiple Myeloma Beijing Chaoyang Hospital (West Hospital), Capital Medical University, Department of Hematology and Oncology References: 1, Jemal A, Siegel R, Ward E et al. Cancer statis, 2009. ca Cancer J clin, 2009;59:225-249 2, Kumar Blood 2008;111:2516-2520. 3.Anderson K C. Multiple myeloma: advances in disease biology,therapeutic implication. Semin Hematol，2001，38(2 suppl 3):6-10 4，Greipp PR, San Miguel J, Durie BG, et al. International staging system for multiple myeloma. J Clin Oncol. 2005;23:3412-3420. 5，Nowakowski GS, Witzig TE, Dingli D, et al. Circulating plasma cells detected by flow cytometry as a predictor of survival in 302 patients with newly diagnosed multiple myeloma. Blood. 2005;106:2276-2279. 6，Tiedemann RE，Mao X,Shi CX,et al.Identification of kinetin riboside as a repressor of CCND1 and CCND2 with preclinical antimyeloma activity.J Clin Invest,2008,118:1750-1764. 7，Fonseca R, Blood E, Rue M, et al. Clinical and biologic implications of recurrent genomic aberrations in myeloma. Blood. 2003;101:4569-4575. 8，Keats JJ, Reiman T, Maxwell CA, et al. In multiple myeloma, t(4;14)(p16;q32) is an adverse prognostic factor irrespective of FGFR3 expression. Blood. 2003;101:1520-1529. 9，Avet-Loiseau H, Attal M, More