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Development of a prognostic model for overall survival in multiple myeloma using the Connect^® MM Patient Registry.

ABSTRACT: Median overall survival (OS) has improved for patients with newly diagnosed multiple myeloma (NDMM), but prognosis varies depending on baseline patient characteristics. Current models use data from selected clinical trial populations, which prevent application to patients in an unselected community setting that reflects routine clinical practice. Using data from the Connect^® MM Registry, a large, US, multicentre, prospective observational cohort study (Cohort 1: 2009-2011; Cohort 2: 2012-2016) of 3011 patients with NDMM, we identified prognostic variables for OS via the multivariable analysis of baseline patient characteristics in Cohort 1 (n = 1493) and developed a tool to examine individual outcomes. Factors associated with OS (n = 1450 treated patients; P < 0·05) were age, del(17p), triplet therapy use, EQ-5D mobility, International Staging System stage, solitary plasmacytoma, history of diabetes, platelet count, Eastern Cooperative Oncology Group performance status and serum creatinine, which were used to create survival matrices for 3- and 5-year OS. The model was internally and externally validated using Connect MM Cohort 2 (Harrell's concordance index, 0·698), MM-015 (0·649), and the phase 3 FIRST (0·647) clinical trials. This novel prognostic tool may help inform outcomes for NDMM in the era of triplet therapy use with novel agents.

SUBMITTER: Terebelo HR

PROVIDER: S-EPMC6899784 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Development of a prognostic model for overall survival in multiple myeloma using the Connect<sup>®</sup> MM Patient Registry.

Terebelo Howard R HR Terebelo Howard R HR Abonour Rafat R Gasparetto Cristina J CJ Toomey Kathleen K Durie Brian G M BGM Hardin James W JW Jagannath Sundar S Wagner Lynne L Narang Mohit M Flick E Dawn ED Srinivasan Shankar S Yue Lihua L Kitali Amani A Agarwal Amit A Rifkin Robert M RM

British journal of haematology 20190805 5

Median overall survival (OS) has improved for patients with newly diagnosed multiple myeloma (NDMM), but prognosis varies depending on baseline patient characteristics. Current models use data from selected clinical trial populations, which prevent application to patients in an unselected community setting that reflects routine clinical practice. Using data from the Connect<sup>®</sup> MM Registry, a large, US, multicentre, prospective observational cohort study (Cohort 1: 2009-2011; Cohort 2: 2 ...[more]

PMID: 31382320

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Project description:Multiple myeloma (MM) is a disease in which abnormal plasma cells proliferate and secrete monoclonal immunoglobulin in the bone marrow. The main characteristic of plasma cells is the expression of the cell surface antigen syndecan-1 (CD138). However, the expression of CD138 is limited to terminally differentiated plasma cells during B cell development. A small subpopulation (2~5%) of human MM cells that lack CD138 expression has been shown to possess enormous proliferation potential in vitro experiment and in animal models, and they also can differentiate into CD138+ plasma cells. Thus, this small subset of MM cells was regarded as myeloma cancer stem cell (MCSC). However, its characteristics associated with the pathogenesis of MM remain unclear. In this study, we analyzed the gene expression data of CD138 cell lines downloaded from Gene Expression Omnibus (GEO) database. Limma package in RStudio was used to identify differentially expressed genes (DEGs). Genes enrichment and protein-protein interaction (PPI) network analysis were performed on DAVID and STRING databases. Furthermore, overall survival (OS) analysis in MM patient was utilized to screen out the hub-genes closely associate with the MM pathogenesis process. Hub-genes expression validation and receiver operating characteristic curve (ROC) analysis was performed in different stages of plasma cell disorder diseases. Finally, we verified these findings in MM patient samples. Through integrated bioinformatics analysis of MM CD138- and CD138+ cell lines, we found that CDC7, CDK1, and CHK1 are highly expressed in CD138- MM cells. These genes are crucial in the G2/M phase of the cell cycle pathway, which is closely related to the malignant proliferation in various tumor cells. Of note, we found that patients with high expression of CDC7, CDK1, and CHK1 had shorter overall survival time. The expression of CHK1 was significantly increased in MM cells compared with normal plasma cell (NPC) and MGUS. More importantly, we further clarified that the expression of CHK1 in release/refraction MM (R/R MM) has obviously increased compared with new diagnosed MM (ND MM).

Dataset Information

Development of a prognostic model for overall survival in multiple myeloma using the Connect^® MM Patient Registry.

Publications

Development of a prognostic model for overall survival in multiple myeloma using the Connect<sup>®</sup> MM Patient Registry.

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Dataset Information

Development of a prognostic model for overall survival in multiple myeloma using the Connect® MM Patient Registry.

Publications

Development of a prognostic model for overall survival in multiple myeloma using the Connect<sup>®</sup> MM Patient Registry.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Development of a prognostic model for overall survival in multiple myeloma using the Connect^® MM Patient Registry.