In the evolving landscape of oncology treatment, patients with Multiple Myeloma (MM) who are ineligible for autologous stem cell transplantation and experience relapse after first-line therapy face significant challenges. The frontline treatment regimen combining daratumumab, lenalidomide, and dexamethasone (DRd) has been a cornerstone in managing MM; however, relapse in this cohort reveals an urgent need for optimized subsequent therapies. A groundbreaking study recently published in the prestigious journal BMC Cancer presents a robust multi-criteria decision analysis (MCDA) framework aimed at refining treatment choice for these post-DRd patients within the Italian healthcare context. This development is set to dramatically influence how clinicians, patients, and policymakers approach therapeutic decision-making in this complex setting.
Multiple myeloma remains a formidable hematologic malignancy characterized by clonal proliferation of plasma cells in the bone marrow. Despite therapeutic advancements, the nature of the disease invariably leads to relapses, significantly complicating management post-initial therapy. The country-specific nuances in treatment availability and reimbursement, especially within European health systems like Italy’s, necessitate a contextualized approach to evaluating therapeutic alternatives. The study at hand uniquely incorporates multiple stakeholder perspectives—hematologists, health economists, decision-makers, and patient representatives—into constructing an inclusive and practical decision framework that transcends traditional clinical endpoints.
The cornerstone of this innovative research lies in the integration of the Measuring Attractiveness by a Categorical-Based Evaluation Technique (MACBETH), an established MCDA method widely endorsed by the International Society for Pharmacoeconomics and Outcomes Research (ISPOR). This methodological choice allows for nuanced quantification of diverse criteria influencing treatment choice, balancing efficacy, safety, costs, and organizational impact. Through systematic data collection, including a meticulous targeted literature review and a multi-stakeholder workshop, researchers identified and refined decision criteria to resonate with real-world relevance and patient-centred concerns.
Delving deeper into the decision metrics, the MCDA framework distilled five pivotal criteria: acquisition cost, clinical efficacy, organizational impact, route of administration, and safety. Notably, safety encompasses six critical adverse events—peripheral neuropathy, diarrhoea, nausea, fatigue, anaemia, and thrombocytopenia—each evaluated to discern their differential impact on treatment preference. This multidimensional assessment captures the real complexities experienced by patients navigating treatment choices that not only influence survival but also quality of life and everyday functioning.
Among these criteria, clinical efficacy emerged robustly as the most weighted consideration, with a median importance of 38.1% according to the stakeholder responses. This hierarchy underscores the primacy of extending survival and achieving disease control in decision-making. Concurrently, safety garnered significant emphasis, constituting a median weight of 26.8%, highlighting the balance clinicians and patients must strike between therapeutic benefit and risk of adverse effects. Peripheral neuropathy stood out as the paramount safety concern, reflecting its profound impact on patient quality of life and treatment adherence.
The comparative evaluation of three therapeutic regimens approved and reimbursed in Italy for lenalidomide-refractory MM patients following DRd relapse revealed striking insights. Selinexor, bortezomib, and dexamethasone (SVd) attained the highest global value score of 72, attributed primarily to its superior efficacy profile across evaluated data sources. Pomalidomide, bortezomib, and dexamethasone (PVd) and carfilzomib and dexamethasone (Kd) followed with scores of 44 and 26, respectively. The differentiation highlights the complex interplay between clinical benefit and safety events, guiding optimal utilization within care pathways.
Crucially, the uniformity of preferences across diverse stakeholders—hematology experts, methodologists, healthcare decision-makers, and patient advocates—signifies broad consensus and lends credibility to the framework’s generalizability and potential for policy influence. This collective approach fosters evidence-based harmonization of treatment guidelines while respecting patient values and system-level feasibility.
The organizational impact criterion incorporated into the MCDA accounted for factors such as resource utilization and treatment logistics, which are increasingly pertinent given the strain on healthcare infrastructures. Considering the route of administration further acknowledges patient convenience and compliance, critical determinants in real-world effectiveness beyond controlled clinical trials.
By methodically combining quantitative analyses and qualitative stakeholder insights, the study anchors its recommendations not only in clinical outcomes but also in real-world practicability and patient-centeredness. This represents a paradigm shift from one-dimensional efficacy evaluation toward holistic, multi-faceted decision-making.
The implications for clinical practice are profound. Hematologists and multidisciplinary care teams can leverage this robust decision framework when deliberating second-line therapies, tailoring choices that harmonize efficacy, safety, economic viability, and patient preferences. For Italian healthcare policymakers and payers, such transparent, systematic analyses underpin rational resource allocation and reimbursement strategies aligned with population health priorities.
Beyond the Italian context, this study serves as a model for other health systems confronting similar therapeutic dilemmas in MM care. The adaptable MCDA approach invites localization while maintaining methodological rigor, promoting optimized, personalized treatment pathways across diverse oncology landscapes.
Moreover, the research stimulates future investigations into expanding decision criteria encompassing long-term patient-reported outcomes, emerging novel agents, and integration of real-world evidence to continuously refine therapeutic algorithms.
Importantly, this study also underscores the criticality of engaging patient voices in complex treatment decisions, ensuring that real-world experience and quality-of-life considerations inform evidence synthesis and guideline development. The incorporation of patient representatives throughout the study process exemplifies best practices in participatory research.
As multiple myeloma treatment options continue to proliferate, frameworks like the one presented are essential to navigate an increasingly complex therapeutic environment. By formalizing decision criteria and transparently weighting their importance, healthcare stakeholders can collectively move toward more rational, justifiable, and patient-aligned care choices.
In summary, this pioneering multi-criteria decision analysis represents a significant advance in supporting treatment decision-making for post-DRd multiple myeloma patients in Italy. It offers a comprehensive, stakeholder-informed, and methodologically sound tool designed to optimize therapeutic selection amidst evolving clinical scenarios. The study not only enriches the scientific dialogue but also directly facilitates improved patient care and health system sustainability in a challenging oncologic domain.
Subject of Research: Treatment decision-making framework for multiple myeloma patients post-first-line therapy with daratumumab, lenalidomide, and dexamethasone (DRd).
Article Title: Supporting treatment decision-making for patients with multiple myeloma post-DRd in Italy: a multi-criteria decision framework.
Article References:
Boccadoro, M., Belotti, A., Bombaci, F. et al. Supporting treatment decision-making for patients with multiple myeloma post-DRd in Italy: a multi-criteria decision framework. BMC Cancer 25, 1676 (2025). https://doi.org/10.1186/s12885-025-15083-y
Image Credits: Scienmag.com
DOI: https://doi.org/10.1186/s12885-025-15083-y
Tags: daratumumab lenalidomide dexamethasone regimenhematologic malignancies managementItalian healthcare system oncologymulti-criteria decision analysis in oncologymultiple myeloma treatment decisionsoncology decision frameworks in Europeoptimizing treatment pathways for myelomapatient-centered care in myelomapost-DRd therapy challengesrelapse management in multiple myelomastakeholder perspectives in healthcare decisionstherapeutic alternatives for myeloma
