Lead Investigator: Ignacio Leiva-Escobar, Heidelberg University Hospital
Title of Proposal Research: TREND-REVIVAL – Trial result extension and disease course modelling to real world evidence generation in multiple myeloma
Vivli Data Request: 10403
Funding Source: The Sanofi iTech Awards Program
Potential Conflicts of Interest: The lead researcher/epidemiologist, Ignacio Leiva-Escobar, is an academic researcher without any commercial interests and is personally funded by the Sanofi iTech Awards Program for the project, which aims to extend RCT inference into real-world settings and explore the disease course through multistate modelling. Ignacio is free to conduct the research independently, and Sanofi has no role in determining how the study will be carried out. Therefore, Ignacio declares funding by the Sanofi iTech Awards Program, but has no further conflicts of interest to declare. In the unlikely case that conflicts of interest arise in the future, they will be declared in any subsequent publication.
Summary of the Proposed Research:
Multiple myeloma (MM) is a type of cancer affecting plasma cells, a white blood cell found in the bone marrow. MM is characterized by the uncontrolled growth of abnormal plasma cells, leading to bone damage, kidney problems, and increased calcium levels. In 2019, approximately 155,688 people worldwide were affected by this health issue. This cancer is most prevalent in people older than 65 years in industrialized countries.
Randomized controlled trials (RCTs) are regularly conducted to determine new effective MM treatments for improving patient survival and quality of life. RCTs are considered the gold standard for proving treatment efficacy such as disease progression and overall survival. Although most patients respond adequately, approximately 20% of newly diagnosed MM patients still experience poor health outcomes. This highlights the need to identify patient characteristics that determine treatment effectiveness (so-called effect modifiers).
RCT findings are relevant to decision-making, but due to their strict inclusion/exclusion criteria, they might not represent the people encountered in clinical care. Additionally, RCT statistical analyses do not consider a transition between multiple states of disease (i.e., a multi-state model), which could provide more comprehensive insights into how people move through different stages of multiple myeloma over time. This would help to map disease progression and guide clinicians when treating patients.
To address the abovementioned issues, the TREND-REVIVAL project aims to enhance real-world evidence by predicting clinical effectiveness from RCT findings and modelling MM trajectory in real-world settings to generate insights for optimizing patient care.
The project will look at two drug combinations: Vrd (i.e., bortozomib + lenalidomide + dexametasone) and Ixazomib-rd (i.e., ixazomib + lenalidomide + dexamethasone). These are therapies are used to treat multiple myeloma by combining cancer drugs together in different ways. They are considered to demonstrate that (1) clinical effectiveness can be predicted from RCT data and (2) a multi-state modelling approach can identify critical disease states. For the first objective, statistical models will be used to extend RCT results to a defined clinical population and explore how specific patient characteristics can modify treatment effects. For the second objective, a multi-state framework will be developed to determine patient disease trajectories and understand how relevant covariates can influence these transitions.
Requested Studies:
Randomized Phase III Trial of Bortezomib, Lenalidomide, and Dexamethasone (VRd) Versus Carfilzomib, Lenalidomide, and Dexamethasone (CRd) Followed by Limited or Indefinite Duration Lenalidomide Maintenance in Patients With Newly Diagnosed Symptomatic Multiple Myeloma (ENDURANCE)
Data Contributor: Project Data Sphere
Study ID: NCT01863550
Sponsor ID: E1A11
A Phase 3, Randomized, Double-Blind, Multicenter Study Comparing Oral Ixazomib (MLN9708) Plus Lenalidomide and Dexamethasone Versus Placebo Plus Lenalidomide and Dexamethasone in Adult Patients With Relapsed and/or Refractory Multiple Myeloma
Data Contributor: Takeda
Study ID: NCT01564537
Sponsor ID: C16010
A Phase 3, Randomized, Double-Blind, Multicenter Study Comparing Oral MLN9708 Plus Lenalidomide and Dexamethasone Versus Placebo Plus Lenalidomide and Dexamethasone in Adult Patients With Newly Diagnosed Multiple Myeloma
Data Contributor: Takeda
Study ID: NCT01850524
Sponsor ID: C160