Development of an Initial Conceptual Model of Multiple Myeloma to Support Clinical and Health Economics Decision Making

Abstract

Background. We aimed to develop and validate a conceptual model of multiple myeloma (MM) that characterizes the attributes affecting disease progression and patient outcomes, and the relationships between them. Methods. Systematic and targeted literature reviews identified disease- and patient-specific attributes of MM that affect disease progression and outcomes. These attributes were validated by a Delphi panel of four international MM experts, and a physician-validated model was constructed. Real-world clinical data from the Czech Registry of Monoclonal Gammopathies (RMG) was used to confirm the relationships between attributes using pairwise correlations and multiple Cox regression analysis. Results. The Delphi panel reached consensus that most cytogenetic abnormalities influenced disease activity, which results in symptoms and complications and affects overall survival (OS). Comorbidities and complications also affect OS. The entire panel agreed that quality of life was influenced by comorbidities, age, complications, and symptoms. Consensus was not reached in some cases, in particular, the influence of del(17p) on complications. The relationships between attributes were confirmed using pairwise analysis of real-world data from the Czech RMG; most of the correlations identified were statistically significant and the strength of the correlations changed with successive relapses. Czech RMG data were also used to confirm significant predictors of OS included in the model, such as age, Eastern Cooperative Oncology Group performance status, and extramedullary disease. Conclusions. This validated conceptual model can be used for economic modeling and clinical decision making. It could also inform the development of disease-based models to explore the impact of disease progression and treatment on outcomes in patients with MM.

Management of Patients with Relapsed and/or Refractory Multiple Myeloma Treated with Novel Combination Therapies in Routine Clinical Practice in Germany

“…In addition, approximately one-third of patients (30%) had hypercalcemia, and around one-quarter of patients (24%) had renal dysfunction at diagnosis. All of these symptoms were slightly higher than our previous study [12] but similar to other reports [16,22,28,29] and highlight their value in aiding decisions on the treatment of patients who are at high risk of disease progression and who would benefit from therapy [30].…”

Novel risk stratification algorithm for estimating the risk of death in patients with relapsed multiple myeloma: external validation in a retrospective chart review

“…A Cox model was developed using a conceptual model in MM which combined a systematic literature review and physician judgement (using a Delphi process) to select candidate predictors, followed by a backward selection process using Akaike's information criterion to identify the independent predictors of overall survival (OS) . 17 HRs for OS of each predictor were derived from the Cox regression analysis. Risk scores were then calculated by multiplying the HRs for each predictor.…”

New Markers of Renal Failure in Multiple Myeloma and Monoclonal Gammopathies

“…Risk stratification algorithms are currently being developed for clinical scenarios (not only at diagnosis but also the initiation of second-line treatment) and involve indices of the individual and disease, e.g., aggressive character and frailty [ 33 ]. Conceptual models for the relationships between disease driving processes, patient characteristics, and key outcomes have been constructed by expert panels and aided by real-world evidence, providing a framework for future research [ 34 ]. Recently, a foundational model has been constructed for processes involved in myeloma-related renal impairment (focusing on proximal tubule injury by FLCs inducing an inflammatory response) [ 35 ].…”