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

Abstract

SummaryMedian 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.

Prognostic and Predictive Factors in Newly Diagnosed Multiple Myeloma Patients with Early Mortality with Prediction Matrix and Three and Five-Year Overall Survival

“…Over the past decade, the adoption of immunomodulatory agents and proteasome inhibitors in triplet therapy extended median OS to greater than 7 years. These gains were predominantly driven by triplet therapy in the elderly and by reducing early mortality in the disease [53,66].…”

“…Furthermore, owing to the selection bias present within clinical trials populations, survival estimates derived from clinical trials limit the applicability to all "Real World" patients. The CONNECT Ò registry was created as a prognostic model for OS in an unselected community and academic setting [66]. Prognostic models should take into account myeloma biology, patient comorbidities and include performance status and mobility assessment [73].…”

Development and Validation of a Novel Prognostic Model for Overall Survival in Newly Diagnosed Multiple Myeloma Integrating Tumor Burden and Comorbidities

“…For example, the UK Myeloma Research Alliance Risk Profile (MRP) taking account of WHO performance status and age, together with ISS stage and C-reactive protein, could help to predict the prognosis and therapy delivery in patients who are not candidates for transplantation ( 19 ). Furthermore, a survival matrix was created using the factors of age, del (17p), triplet therapy use, EQ-5D mobility, ISS stage, solitary plasmacytoma, history of diabetes, platelet count, Eastern Cooperative Oncology Group performance status, and serum creatinine for predicting the outcomes of NDMM patients ( 20 ). Moreover, a pleural effusion-based nomogram including factors of pleural effusion, plasma cell proportion in the bone marrow, ISS stage, Charlson Comorbidity Index (CCI), 1q21 gain, and autologous hematopoietic stem cell transplantation (HSCT) ( 21 ) was also performed to evaluate the prognosis in unselected MM population.…”

New insights into genetic characteristics between multiple myeloma and COVID‐19: An integrative bioinformatics analysis of gene expression omnibus microarray and the cancer genome atlas data

“…In hematological malignancies, the incidence of MM ranks second to non‐Hodgkin lymphoma. The incidence rate of MM is 2.1 per 100 000 persons globally and is higher (10 per 100,000 persons) in Latin American countries 2–5 . The survival rate of MM patients has been greatly improved over the past two decades with the introduction of new drugs, but MM remains an incurable malignancy.…”

“…The incidence rate of MM is 2.1 per 100 000 persons globally and is higher (10 per 100,000 persons) in Latin American countries. 2 , 3 , 4 , 5 The survival rate of MM patients has been greatly improved over the past two decades with the introduction of new drugs, but MM remains an incurable malignancy. Also, the 5‐year and 10‐year overall survival rate of MM is still less than 60% and 40%.…”