Identification of treatment effect modifiers and prognostic factors in newly diagnosed and relapsed or refractory multiple myeloma
Publication: Journal of Comparative Effectiveness Research
Abstract
Aim: We aimed to identify variables that affect the prognosis and treatment effect in multiple myeloma (MM). Materials & methods: Published literature of randomized controlled trials (RCTs) and population-adjusted indirect comparisons (PAICs) in newly diagnosed (ND) and relapsed/refractory (RR) MM populations reporting overall survival (OS) and progression-free survival (PFS) were identified. Possible treatment effect modifiers (TEMs) were evaluated based on the ratio between effect estimates of different strata within subgroups for OS and PFS among eligible RCTs. Potential prognostic factors (PFs) were identified using the lists of covariates adjusted for in PAICs meeting the eligibility criteria. Results: Sixty-five RCTs and 59 PAICs were included for synthesis. In ND-MM and RR-MM patients, age, sex, International Staging System stage, and cytogenetics were identified as potential TEMs for PFS based on data from published RCTs. Refractory disease, prior therapy exposure status and creatinine clearance were additional TEMs for PFS in RR-MM patients. Eastern Cooperative Oncology Group performance score and creatinine clearance were TEM candidates of PFS for ND-MM stem-cell transplant-ineligible patients. No consistent TEMs for OS were identified across all MM populations. Commonly adjusted variables for both OS and PFS in published PAICs of all populations aligned with potential TEMs of PFS identified in published RCTs. Additionally, subtype of MM, time since diagnosis and extramedullary disease or presence of plasmacytoma were common variables for adjustment in PAICs evaluating RR-MM. Frequency of each variable adjusted for differs by population and outcome. Only one PAIC reported TEMs separately from PFs. Conclusion: TEMs and PFs identified herein can help inform future clinical trial design and serve as a primer when conducting PAICs evaluating OS and PFS in ND/RR-MM.
Plain language summary: identification of patient characteristics that affect treatment effectiveness in multiple myeloma
What is this article about?
Multiple myeloma (MM) is a cancer of the blood that has remained an incurable disease. Rapid technological advances have introduced numerous new therapeutic classes that improve survival. Randomized controlled trials (RCTs) are the gold standard study. However, complex treatment landscapes can pose practical challenges in directly comparing the effectiveness of novel regimens against all available standard of care drug regimens in head-to-head clinical trials. In the absence of head-to-head RCT data, indirect treatment comparison (ITC) is another way to compare the relative effectiveness of alternative treatments that have been studied in separate clinical trials. Prior to conducting RCTs and ITCs, patient characteristics that may affect outcomes or influence the magnitude of the treatment effect should be identified. Reviews of publications across multiple MM populations were conducted to identify such patient characteristics.
What were the results?
Ten characteristics related to patient demographics, disease severity, prior therapy exposure and laboratory values were considered likely to influence treatment effectiveness across different MM populations.
Why is this important?
Results from this research can help inform future ITCs and clinical trials in MM.
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Received: 12 December 2024
Accepted: 8 July 2025
Published online: 12 August 2025
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Identification of treatment effect modifiers and prognostic factors in newly diagnosed and relapsed or refractory multiple myeloma. (2025) Journal of Comparative Effectiveness Research. DOI: 10.57264/cer-2024-0180
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