Multiple myeloma in elderly patients—a Portuguese multicentric real-life study

J of Cellular Biochemistry

Zhang

Huang

et al. 2019

This study examined the underlying mechanism of miR‐215‐5p in multiple myeloma (MM) at the molecular level. miR‐215‐5p was upregulated in bone marrow specimens of patients with MM and MM cell lines through real‐time polymerase chain reaction, and downregulation of miR‐215‐5p was related to poor survival of patients with MM. The results of Western blot assay showed that the PI3K/AKT/mTOR signaling pathway was activated in bone marrow specimens of patients with MM. miR‐215‐5p was found to negatively correlate with runt‐related transcription factor 1 (RUNX1) expression in MM clinical bone marrow samples. Therefore, to test the probable mechanisms of the regulation of MM cell proliferation and apoptosis, a miR‐215‐5p mimics/inhibitors/negative control was transfected into MM cells. The targets of miR‐215‐5p were estimated using four bioinformatics databases (including miRDB, miRTarBase, Starbase, and Targetscan). Furthermore, enrichment analyses of gene ontology and Kyoto Encyclopedia of Genomes pathway were carried out at the Enrichr website. Cell viability was detected using the MTT method, while apoptosis and cell cycle were measured using flow cytometry. RUNX1, CDK2, CDC25B, cleaved‐caspase‐3, cleaved‐PARP, p‐PI3K, PI3K, p‐AKT, AKT, p‐mTOR as well as mTOR protein were also investigated using Western blot analysis. According to our findings, miR‐215‐5p overexpression could induce apoptosis while rendering cell cycle arrest at G1 phase and reducing the proliferation of cells. Meanwhile, miRNA‐215‐5p could negatively regulate messengerRNA and protein levels of RUNX1 in MM cells. In addition, there was a similar effect in cell proliferation and apoptosis after miR‐215‐5p mimics or siRNA‐RUNX1 transfection. miR‐215‐5p inhibition inhibited apoptosis while increased the phosphorylation levels of PI3K, AKT, and mTOR proteins, whereas, miR‐215‐5p overexpression increased cell proliferation. Therefore, miR‐215‐5p inhibited MM cell apoptosis via targeting RUNX1 and suppressing the activation of the PI3K/AKT/mTOR pathway.

Section: Introductionmentioning

confidence: 99%

miR‐215‐5p is an anticancer gene in multiple myeloma by targeting RUNX1 and deactivating the PI3K/AKT/mTOR pathway

J of Cellular Biochemistry

Zhang

Huang

et al. 2019

“…In this study there were no differences in OS among patients treated with different first‐line induction regimen, which is different from previous real‐world reports. 5 , 6 We supposed it may be related to the regimen heterogeneity in different studies. Considering the clinical benefit of Dara‐Rd in transplant‐ineligible MM patients regardless of frailty status in clinical trial, it is worthy to explore the combination of daratumumab to the PIs or IMiDs regimens in elderly patients for further survival improvement in real world .…”

Section: Discussionmentioning

confidence: 99%

“…Up till now quite few relevant real‐world studies have been conducted on elderly subpopulation with MM, mostly from Europe and North America. 5 , 6 , 7 There is a lack of data on treatment patterns and survival of elderly Asian patients. In China, novel agents such as bortezomib, ixazomib, and lenalidomide, have been reimbursed by medical insurance system after 2016, which brought advantages of clinical availability.…”

Section: Introductionmentioning

confidence: 99%

Front‐line treatment efficacy and clinical outcomes of elderly patients with multiple myeloma in a real‐world setting: A multicenter retrospective study in China

Cui

et al. 2022

Cancer Medicine

Background The use of proteasome inhibitors (PIs), new immune modulators (IMiDs), and other new drugs, as well as high‐dose chemotherapy combined with autologous stem cell transplantation has considerably improved the survival of young patients with multiple myeloma (MM). However, the improvement in survival among elderly patients remains insufficient. Optimal treatment recommendation models for elderly patients with MM have not been developed especially there are quite few study in the real world. Methods We retrospectively analyzed the treatment patterns and outcomes of 328 Chinese patients (≥65 years) with MM in a real‐world setting. Patients were divided into three groups according to induction regimens. Results The median age of the cohort was 70 (65–86) years. The patients were divided into group 1 (PIs based regimens, n = 218), group 2 (IMiDs based regimens, n = 48) and group 3 (PIs + IMiDs, n = 62). Induction regimens in group 3 produced higher overall response rate than group 1 and 2 (85.42% vs. 71.08% vs. 66.67%, p = 0.016). The median follow‐up of the cohort was 30 (interquartile range [IQR] 18–36) months. For the entire cohort median progression‐free survival (PFS) was 26 (IQR 12.00–42.89) months and overall survival (OS) was 60 (IQR 40.00–67.20) months. The PFS were not significantly different among the three groups (28 months vs. 18 months vs. 26 months, p = 0.182). So were the OS (60 months vs. 59 months vs. not reached, p = 0.067). Multivariate analysis revealed that age >70 year, frailty status (Geriatric vulnerability score), induction efficacy < partial remission, and no maintenance treatment were independent poor prognostic factors for OS. Conclusion Front‐line induction regimens combining PIs and IMiDs developed more deep response than single PI or IMiD based regimens. Maintenance treatment can further improve the clinical outcome in elderly MM patients in real‐world setting.

“…Immunomodulatory drugs such as lenalidomide and pomalidomide, proteasome inhibitors such as bortezomib, autologous stem cell transplantation, and monoclonal antibodies have significantly improved the survival rate of MM patients [ 6 , 7 ], but recurrence and resistance are still a major problem [ 8 ]. The staging and classification of MM have always been the key to MM individualized precision therapy.…”

Section: Introductionmentioning

confidence: 99%

An interactive nomogram based on clinical and molecular signatures to predict prognosis in multiple myeloma patients

Dai

et al. 2021

Aging

Although novel drugs and treatments have been developed and improved, multiple myeloma (MM) is still recurrent and difficult to cure. In the present study, the magenta module containing 400 hub genes was determined from the training dataset of GSE24080 through weighted gene co-expression network analysis (WGCNA). Then, using the least absolute shrinkage and selection operator (Lasso) analysis, a fifteen-gene signature was firstly selected and the predictive performance for overall survival (OS) was favorable, which was identified by Receiver Operating Characteristic (ROC) curves. The risk score model was constructed based on survival-associated fifteen genes from the Lasso model, which classified MM patients into high-risk and low-risk groups. Areas under the curve (AUC) of ROC curve and log-rank test showed that the high-risk group was correlated to the dismal survival outcome of MM patients, which was also identified in testing dataset of GSE9782. The calibration plot, the AUC value of the ROC curve and Concordance-index showed that the interactive nomogram with risk score could favorably predict the probability of multi-year OS of MM patients. Therefore, it may help clinicians make a precise therapeutic decision based on the easy-to-use tool of the nomogram.