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

Howard R Terebelo, Rafat Abonour, Cristina J Gasparetto, Kathleen Toomey, Brian G M Durie, James W Hardin, Sundar Jagannath, Lynne Wagner, Mohit Narang, E Dawn Flick, Shankar Srinivasan, Lihua Yue, Amani Kitali, Amit Agarwal, Robert M Rifkin, CONNECT MM Registry Investigators, Howard R Terebelo, Rafat Abonour, Cristina J Gasparetto, Kathleen Toomey, Brian G M Durie, James W Hardin, Sundar Jagannath, Lynne Wagner, Mohit Narang, E Dawn Flick, Shankar Srinivasan, Lihua Yue, Amani Kitali, Amit Agarwal, Robert M Rifkin, CONNECT MM Registry Investigators

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.

Keywords: matrix; myeloma; prognosis; registry; survival.

Conflict of interest statement

This study was funded by Celgene Corporation. HRT provided consultancy services to Celgene and participated in speakers’ bureaus for Janssen, Takeda and Pharmacyclics LLC, an AbbVie Company. RA is a member of steering committees for Celgene and Takeda, has received research funding from Celgene and Takeda, and has received research funding from Prothena. CJG has received honoraria from Janssen, Bristol‐Myers Squibb, Celgene and Takeda; provided consultancy services to Janssen, Bristol‐Myers Squibb and Celgene; received travel reimbursement from Janssen, Bristol‐Myers Squibb and Celgene; and received research funding from Celgene. KT provided consultancy services to Celgene, participated in speakers’ bureaus for Myriad Genetics, and received travel reimbursement from Dava Oncology. BGMD provided consultancy services to Takeda and Janssen. JWH provided consultancy services to Celgene. SJ provided consultancy services to Celgene, Bristol‐Myers Squibb, Novartis and Merck, and participated in speakers’ bureaus for MMRF and Medicom. LW provided consultancy services to EveryFit, Gilead and Janssen. MN provided consultancy services and participated in speakers’ bureaus for Celgene and participated in speakers’ bureaus for Janssen. EDF, SS, LY, AK and AA are employed by Celgene. RMR provided consultancy services to Amgen, Boehringer Ingelheim, Celgene, EMD Serono, Sandoz and Takeda, and owns stocks with McKesson.

© 2019 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.

Figures

Figure 1
Figure 1
Three‐year overall survival matrix for patients aged (A) ≤75 years and (B) >75 years. Creat, creatinine (µmol/l); ECOG, Eastern Cooperative Oncology Group performance status; ISS, International Staging System; N, no; PC, platelet count (×109/l); Y, yes.
Figure 2
Figure 2
Five‐year overall survival matrix for patients aged ≤75 years (A) and >75 years (B). Creat, creatinine (µmol/l); ECOG, Eastern Cooperative Oncology Group performance status; ISS, International Staging System; N, no; PC, platelet count (×109/l); Y, yes.
Figure 3
Figure 3
External validation models graphing actual versus estimated probabilities against (A) Connect MM Cohort 2, (B) MM‐015 and (C) MM‐020/FIRST data. The filled circles represent observations in groups (ordered from most probable to least probable) for whom the actual probabilities (from Cohort 2, MM‐015 or FIRST trial data) are plotted against the estimated probabilities (based on the Connect MM Cox model). The dotted line and the curved solid line (nonparametric curve) are the fitted curves for the plot of actual and estimated probabilities. Harrell's concordance index (concordance probability; C‐Index) is the probability that a randomly selected pair of patients in the independent external data set (1 with a poorer survival outcome than the other) will be correctly differentially identified based on entering the baseline characteristics of the 2 patients in the fitted model (Steyerberg et al, 2010).

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