Next-Generation Biomarkers in Multiple Myeloma: Understanding the Molecular Basis for Potential Use in Diagnosis and Prognosis

Soliman, Amro M.; Das, Srijit; Teoh, Seong Lin

doi:10.3390/ijms22147470

Cited by 18 publications

(20 citation statements)

References 175 publications

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“…The inclusion criteria were as follows: (1) All of the MM patients meet the diagnostic criteria of the International Myeloma Working Group (IMWG); (2) All patients were newly diagnosed MM at the time of inclusion; (3) whole-body diffusion-weighted imaging (WB-DWI) was performed before treatment; (4) The interval between initial chemotherapy and WB-DWI was within 1 week; (5) All the patients enrolled were symptomatic or active MM with detectable M protein in blood or urine; (6) All the patients received at least four courses of firstline treatment based on bortezomib, and the treatment response was evaluated; (7) All patients received regular (every 3 months) inpatient services, outpatient services, and telephone follow-up.…”

Section: Patientsmentioning

confidence: 99%

“…The overall survival (OS) of MM patients was 30 months. Thalidomide treatment could prolong the OS to 46 months and bone marrow transplantation to 48 months (7). Although with the change of treatment methods the 5-year survival rate of MM has increased from 28% to 56% (1975 to 2012) (5), the imaging methods that can effectively predict the prognosis of the disease still need to be explored.…”

Section: Introductionmentioning

confidence: 99%

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The Apparent Diffusion Coefficient of Diffusion-Weighted Whole-Body Magnetic Resonance Imaging Affects the Survival of Multiple Myeloma Independently

et al. 2022

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BackgroundDiffusion-weighted whole-body MRI (DW-MRI) is increasingly used to evaluate bone diseases of multiple myeloma (MM), but there is lack of quantitative indicator for DW-MRI to reflect the prognosis of MM. Apparent diffusion coefficient (ADC) values in DW-MRI has potential correlations between some indexes of MM, but the influence of ADC on MM survival needs to be further verified.MethodsA total of 381 newly diagnosed MM patients were enrolled in the study to analyze the effect of ADC values in DW-MRI on progression-free survival (PFS) and overall survival (OS). The Kaplan–Meier method was used to perform univariate survival analysis, and the Cox proportional hazards model was used for multivariate analysis. In addition to the ADC value, genetic and serological indexes were also included.ResultsThe survivals were observed in univariate ADC stratification with median PFS of 52.0, 45.0, 34.0, and 26.0 months (the unit of ADC value was 10−3 mm2/s; the ADC ranges were ADC < 0.4886, 0.4886 ≤ ADC < 0.6545, 0.6545 ≤ ADC < 0.7750, and ADC ≥ 0.7750; 95% CI, 43.759–62.241, 46.336–53.664, 39.753–46.247, and 27.812–32.188). The OS were 81.0, 61.0, 47.0, and 36.0 months (p < 0.001; 95% CI, 71.356–82.644, 67.630–70.370, 57.031–60.969, and 36.107–43.893). In Cox proportional hazards model, the ADC value was considered to be an independent risk factor affecting PFS and OS of MM (both p < 0.001).ConclusionsThis study supports that ADC in DW-MRI may independently stratify MM patients and better predict their prognosis. The combined use of DW-MRI and other parameters allows more accurate evaluation of MM survival.Trial Registrationhttp://www.chictr.org.cn/showproj.aspx?proj=49012, ChiCTR2000029587.

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Section: Patientsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Apparent Diffusion Coefficient of Diffusion-Weighted Whole-Body Magnetic Resonance Imaging Affects the Survival of Multiple Myeloma Independently

et al. 2022

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“… 20 , 26 In recent years, NGS technology, which involves whole-exome sequencing, has been used to identify the genomic mutation landscape and clonal heterogeneity in MM. 27 – 29 There is an MM-specific gene panel for targeting NGS sequencing (M 3 P v3.0) that includes 88 frequently mutated genes and drug-related genes. 30 Although the genomic complexity of MM disease has been extensively studied in Western countries, data on Southeast Asian populations are still lacking.…”

Section: Introductionmentioning

confidence: 99%

Comparison of Clinical Characteristics and Genetic Aberrations of Plasma Cell Disorders in Thailand Population

Jirabanditsakul

Dakeng

Kunacheewa

et al. 2022

Technol Cancer Res Treat

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Multiple myeloma is an incurable malignancy of plasma cells resulting from impaired terminal B cell development. Almost all patients with multiple myeloma eventually have a relapse. Many studies have demonstrated the importance of the various genomic mutations that characterize multiple myeloma as a complex heterogeneous disease. In recent years, next-generation sequencing has been used to identify the genomic mutation landscape and clonal heterogeneity of multiple myeloma. This is the first study, a prospective observational study, to identify somatic mutations in plasma cell disorders in the Thai population using targeted next-generation sequencing. Twenty-seven patients with plasma cell disorders were enrolled comprising 17 cases of newly diagnosed multiple myeloma, 5 cases of relapsed/refractory multiple myeloma, and 5 cases of other plasma cell disorders. The pathogenic mutations were found in 17 of 27 patients. Seventy percent of those who had a mutation (12/17 patients) habored a single mutation, whereas the others had more than one mutation. Fifteen pathogenic mutation genes were identified: ATM, BRAF, CYLD, DIS3, DNMT3A, FBXW7, FLT3, GNA13, IRF4, KMT2A, NRAS, SAMHD1, TENT5C, TP53, and TRAF3. Most have previously been reported to be involved in the RAS/MAPK pathway, the nuclear factor kappa B pathway, the DNA-repair pathway, the CRBN pathway, tumor suppressor gene mutation, or an epigenetic mutation. However, the current study also identified mutations that had not been reported to be related to myeloma: GNA13 and FBXW7. Therefore, a deep understanding of molecular genomics would inevitably improve the clinical management of plasma cell disorder patients, and the increased knowledge would ultimately result in better outcomes for the patients.

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“…At this point, the clinical and laboratory criteria utilized for building the score systems above cannot comprehensively capture the molecular and biological indicators underlying the resistance machinery of new treatments and, ultimately, the PFS and OS magnitude. In this respect, the use of different analytical methods to establish a comprehensive prognostic scoring system, including gene expression/mutation-derived risk scores and clinical prognostic signatures, is desirable to improve predictive precision and guide future clinical therapy ( 46 , 47 ). Nevertheless, next-generation markers are far from their systematic utilization in RRMM real-world patients.…”

Section: Discussionmentioning

confidence: 99%

Survival Risk Scores for Real-Life Relapsed/Refractory Multiple Myeloma Patients Receiving Elotuzumab or Carfilzomib In Combination With Lenalidomide and Dexamethasone as Salvage Therapy: Analysis of 919 Cases Outside Clinical Trials

et al. 2022

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The present study aimed to develop two survival risk scores (RS) for overall survival (OS, SRSKRd/EloRd) and progression-free survival (PFS, PRSKRd/EloRd) in 919 relapsed/refractory multiple myeloma (RRMM) patients who received carfilzomib, lenalidomide, and dexamethasone (KRd)/elotuzumab, lenalidomide, and dexamethasone (EloRd). The median OS was 35.4 months, with no significant difference between the KRd arm versus the EloRd arm. In the multivariate analysis, advanced ISS (HR = 1.31; P = 0.025), interval diagnosis–therapy (HR = 1.46; P = 0.001), number of previous lines of therapies (HR = 1.96; P < 0.0001), older age (HR = 1.72; P < 0.0001), and prior lenalidomide exposure (HR = 1.30; P = 0.026) remained independently associated with death. The median PFS was 20.3 months, with no difference between the two strategies. The multivariate model identified a significant progression/death risk increase for ISS III (HR = 1.37; P = 0.002), >3 previous lines of therapies (HR = 1.67; P < 0.0001), older age (HR = 1.64; P < 0.0001), and prior lenalidomide exposure (HR = 1.35; P = 0.003). Three risk SRSKRd/EloRd categories were generated: low-risk (134 cases, 16.5%), intermediate-risk (467 cases, 57.3%), and high-risk categories (213 cases, 26.2%). The 1- and 2-year OS probability rates were 92.3% and 83.8% for the low-risk (HR = 1, reference category), 81.1% and 60.6% (HR = 2.73; P < 0.0001) for the intermediate-risk, and 65.5% and 42.5% (HR = 4.91; P < 0.0001) for the high-risk groups, respectively. Notably, unlike the low-risk group, which did not cross the median timeline, the OS median values were 36.6 and 18.6 months for the intermediate- and high-risk cases, respectively. Similarly, three PRSKRd/EloRd risk categories were engendered. Based on such grouping, 338 (41.5%) cases were allocated in the low-, 248 (30.5%) in the intermediate-, and 228 (28.0%) in the high-risk groups. The 1- and 2-year PFS probability rates were 71.4% and 54.5% for the low-risk (HR = 1, reference category), 68.9% and 43.7% (HR = 1.95; P < 0.0001) for the intermediate-risk, and 48.0% and 27.1% (HR = 3.73; P < 0.0001) for the high-risk groups, respectively. The PFS median values were 29.0, 21.0, and 11.7 months for the low-, intermediate-, and high-risk cases. This analysis showed 2.7- and 4.9-fold increased risk of death for the intermediate- and high-risk cases treated with KRd/EloRd as salvage therapy. The combined progression/death risks of the two categories were increased 1.3- and 2.2-fold compared to the low-risk group. In conclusion, SRSKRd/EloRd and PRSKRd/EloRd may represent accessible and globally applicable models in daily clinical practice and ultimately represent a prognostic tool for RRMM patients who received KRd or EloRd.

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Next-Generation Biomarkers in Multiple Myeloma: Understanding the Molecular Basis for Potential Use in Diagnosis and Prognosis

Cited by 18 publications

References 175 publications

The Apparent Diffusion Coefficient of Diffusion-Weighted Whole-Body Magnetic Resonance Imaging Affects the Survival of Multiple Myeloma Independently

The Apparent Diffusion Coefficient of Diffusion-Weighted Whole-Body Magnetic Resonance Imaging Affects the Survival of Multiple Myeloma Independently

Comparison of Clinical Characteristics and Genetic Aberrations of Plasma Cell Disorders in Thailand Population

Survival Risk Scores for Real-Life Relapsed/Refractory Multiple Myeloma Patients Receiving Elotuzumab or Carfilzomib In Combination With Lenalidomide and Dexamethasone as Salvage Therapy: Analysis of 919 Cases Outside Clinical Trials

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