Abstract Current standard predictive models of disease risk do not adequately account for the heterogeneity of survival outcomes in patients with new‐diagnosed multiple myeloma (NDMM). In this retrospective, multicohort study, we collected clinical and genetic data from 1792 NDMM patients and identified the prognostic impact of all features. Using the top‐ranked predictive features, a weighted Myeloma Prognostic Score System (MPSS) risk model was formulated and validated to predict overall survival (OS). In the training cohort, elevated lactate dehydrogenase level (LDH), International Staging System (ISS) Stage III, thrombocytopenia, and cumulative high‐risk cytogenetic aberration (HRA) numbers were found to have independent prognostic significance. Each risk factor was defined as its weighted value respectively according to their hazard ratio for OS (thrombocytopenia 2, elevated LDH 1, ISS III 2, one HRA 1, and ≥2 HRA 2, points). Patients were further stratified into four risk groups: MPSS I (22.5%, 0 points), II (17.6%, 1 points), III (38.6%, 2–3 points), and IV (21.3%, 4–7 points). MPSS risk stratification showed optimal discrimination, as well as calibration, of four risk groups with median OS of 91.0, 69.8, 45.0, and 28.0 months, for patients in MPSS I to IV groups ( p < .001), respectively. Importantly, the MPSS model retained its prognostic value in the internal validation cohort and an independent external validation cohort, and exhibited significant risk distribution compared with conventional prognostic models (R‐ISS, R2‐ISS, and MASS). Utilization of the MPSS model in clinical practice could improve risk estimation in NDMM patients, thus prompting individualized treatment strategies.

10.1002/ajh.27207

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Citations (8)

The Incidence, Clinical Application and Prognostic Significance of MYD88 and CXCR4 Mutation in Chinese Patients with Lymphoplasmacytic Lymphoma/ Waldenström Macroglobulinemia

Blood (2023)

Ying Yu Yuting Yan Jun Wang Wenjie Xiong Yao Yao

Sanger sequencing

Lymphoplasmacytic Lymphoma

Macroglobulinemia

10.1182/blood-2023-188786

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1クラス超球サポートベクターマシン(SVM)による機械の故障診断

Zhendong Gongcheng Xuebao (2008)

Ziying Wang Mianhao Qiu Gang An Kai Wang

Source

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Monitoring minimal residual disease in patients with multiple myeloma by targeted tracking serum M-protein using mass spectrometry (EasyM)

Clinical Cancer Research (2024)

Huishou Fan Bing Wang Lihui Shi Ni Pan Wenqiang Yan

Abstract Purpose: We investigated both the clinical utilities and the prognostic impacts of the clonotypic peptide mass spectrometry (MS)-EasyM, a blood-based minimal residual disease (MRD) monitoring protocol in multiple myeloma. Experimental Design: A total of 447 sequential serum samples from 56 patients with multiple myeloma were analyzed using EasyM. Patient-specific M-protein peptides were sequenced from diagnostic samples; sequential samples were quantified by EasyM to monitor the M-protein. The performance of EasyM was compared with serum immunofixation electrophoresis (IFE), bone marrow multiparameter flow cytometry (MFC), and next-generation flow cytometry (NGF) detection. The optimal balance of EasyM sensitivity/specificity versus NGF (10−5 sensitivity) was determined and the prognostic impact of MS-MRD status was investigated. Results: Of the 447 serum samples detected and measured by EasyM, 397, 126, and 92 had time-matching results for comparison with serum IFE, MFC-MRD, and NGF-MRD, respectively. Using a dotp >0.9 as the MS-MRD positive, sensitivity was 99.6% versus IFE and 100.0% versus MFC and NGF. Using an MS negative cutoff informed by ROC analysis (<1.86% of that at diagnosis), EasyM sensitivity remained high versus IFE (88.3%), MFC (85.1%), and NGF (93.2%), whereas specificity increased to 90.4%, 55.8%, and 93.2%, respectively. In the multivariate analysis, older diagnostic age was an independent predictor for progression-free survival [PFS; high risk (HR), 3.15; 1.26–7.86], the best MS-MRD status (MS-MRD negative) was independent predictor for both PFS (HR, 0.25; 0.12–0.52) and overall survival (HR, 0.16; 0.06–0.40). Conclusions: EasyM is a highly sensitive and minimal invasive method of MRD monitoring in multiple myeloma; MS-MRD had significant predictive ability for survival outcomes.

Minimal Residual Disease

Serum protein electrophoresis

Immunofixation

10.1158/1078-0432.ccr-23-2767

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Citations (2)

Identification of Myeloma-Initiating Cells By Single-Cell RNA Sequencing

Blood (2021)

Lixin Gong Hao Sun Junqiang Lv Xiaojing Wei Lanting Liu

Circulating tumor cell

Tumor progression

KLF4

Gene signature

10.1182/blood-2021-148275

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Identification of Therapy-Induced Clonal Evolution and Resistance Pathways in Minimal Residual Clones in Multiple Myeloma through Single-Cell Sequencing

Clinical Cancer Research (2024)

Jian Cui Xiaoyun Li Shuhui Deng Chenxing Du Huishou Fan

Abstract Purpose: In multiple myeloma (MM), therapy-induced clonal evolution is associated with treatment resistance and is one of the most important hindrances toward a cure for MM. To further understand the molecular mechanisms controlling the clonal evolution of MM, we applied single-cell RNA sequencing (scRNA-seq) to paired diagnostic and posttreatment bone marrow (BM) samples. Experimental Design: scRNA-seq was performed on 38 BM samples from patients with monoclonal gammopathy of undetermined significance (n = 1), MM patients at diagnosis (n = 19), MM posttreatment (n = 17), and one healthy donor (HD). The single-cell transcriptome data of malignant plasma cells (PC) and the surrounding immune microenvironment were analyzed. Results: Profiling by scRNA-seq data revealed three primary trajectories of transcriptional evolution after treatment: clonal elimination in patients with undetectable minimal residual disease (MRD−) and clonal stabilization and clonal selection in detectable MRD (MRD+) patients. We noted a metabolic shift toward fatty acid oxidation in cycling-resistant PCs, whereas selective PCs favored the NF-κB pathway. Intriguingly, when comparing the genetic and transcriptional dynamics, we found a significant correlation between genetic and nongenetic factors in driving the clonal evolution. Furthermore, we identified variations in cellular interactions between malignant PCs and the tumor microenvironment. Selective PCs showed the most robust cellular interactions with the tumor microenvironment. Conclusions: These data suggest that MM cells could rapidly adapt to induction treatment through transcriptional adaptation, metabolic adaptation, and specialized immune evasion. Targeting therapy-induced resistance mechanisms may help to avert refractory disease in MM.

Identification

Minimal Residual Disease

10.1158/1078-0432.ccr-24-0545

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Citations (2)

Structural Basis for Androgen Receptor Interdomain and Coactivator Interactions Suggests a Transition in Nuclear Receptor Activation Function Dominance

Molecular Cell (2004)

Bin He Robert T. Gampe A.J. Kole Andrew T. Hnat Thomas B. Stanley

Subfamily

10.1016/j.molcel.2004.09.036

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Citations (283)

Multiple Myeloma Cell Defects Erythropoiesis and Results Anemia Via High Level of CCL3 in Bone Marrow Microenvironment

Blood (2020)

Lanting Liu Zhen Yu Hui Cheng Weiwei Sui Shuhui Deng

10.1182/blood-2020-139006

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TABLE 2 from Clinical Benefit of Autologous Stem Cell Transplantation for Patients with Multiple Myeloma Achieving Undetectable Minimal Residual Disease after Induction Treatment

Jiahui Liu Wenqiang Yan Huishou Fan Jingyu Xu Lingna Li

Multivariate analyses of PFS and OS in 407 patients with transplant-eligible myeloma

Minimal Residual Disease

Autologous stem-cell transplantation

Table (database)

10.1158/2767-9764.24092401.v1

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FIGURE 1 from Clinical Benefit of Autologous Stem Cell Transplantation for Patients with Multiple Myeloma Achieving Undetectable Minimal Residual Disease after Induction Treatment

Jiahui Liu Wenqiang Yan Huishou Fan Jingyu Xu Lingna Li

The impact of ASCT and early MRD status on prognosis. Impact of early MRD-negative status on PFS (A) and impact of early MRD-negative status on OS (B); impact of ASCT by different MRD status on PFS (C); impact of ASCT by different MRD status on OS (D). ASCT: autologous stem-cell transplant; early MRD status: MRD status after induction treatment; NR: not reached; NS: not significant; OS: overall survival; PFS: progression-free survival; *, P < 0.05; **, P < 0.01; ***, P < 0.001.

Minimal Residual Disease

Autologous stem-cell transplantation

10.1158/2767-9764.24092431.v1

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