Dataset Information

Treatment Regimens for Transplant-Ineligible Patients With Newly Diagnosed Multiple Myeloma: A Systematic Literature Review and Network Meta-analysis.

ABSTRACT:

Introduction

Many treatment regimens have been evaluated in transplant-ineligible (TIE) patients with newly diagnosed multiple myeloma (NDMM). The objective of this study was to compare the efficacy of relevant therapies for the treatment of TIE patients with NDMM.

Methods

Progression-free survival (PFS) and overall survival (OS) from large randomised controlled trials (RCTs) evaluating different treatment options for TIE patients with NDMM were compared in a network meta-analysis (NMA). The NMA includes recent primary and long-term OS readouts from SWOG S0777, ENDURANCE, MAIA, and ALCYONE. Relevant trials were identified through a systematic literature review. Relative efficacy measures (i.e., hazard ratios [HRs] for PFS and OS) were extracted and synthesised in random-effects NMAs.

Results

A total of 122 publications describing 45 unique RCTs was identified. Continuous lenalidomide/dexamethasone (Rd) was selected as the referent comparator. Daratumumab-containing treatments (daratumumab/lenalidomide/dexamethasone [D-Rd], daratumumab/bortezomib/melphalan/prednisone [D-VMP]) and bortezomib/lenalidomide/dexamethasone (VRd) had the highest probabilities of being more effective than Rd continuous for PFS (HR: D-Rd, 0.53; D-VMP, 0.57, VRd, 0.77) and OS (HR: D-Rd, 0.68; VRd, 0.77, D-VMP, 0.78). D-Rd had the highest chance of being ranked as the most effective treatment with respect to PFS and OS. Results using a smaller network focusing on only those regimens that are relevant in Europe were consistent with the primary analysis.

Conclusions

These comparative effectiveness data may help inform treatment selection in TIE patients with NDMM.

SUBMITTER: Facon T

PROVIDER: S-EPMC9056460 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background and objectiveThis study aimed to assess the cost-effectiveness of two regimens regarded as the standard of care for the treatment of newly diagnosed, transplant-ineligible multiple myeloma in Singapore: (1) daratumumab, lenalidomide, and dexamethasone and (2) bortezomib, lenalidomide, and dexamethasone. Additionally, it aimed to explore potential strategies to manage decision uncertainty and mitigate financial risk.MethodsA cost-effectiveness analysis from the healthcare system perspective was conducted using a partitioned survival model to estimate lifetime costs and quality-adjusted life years (QALYs) associated with daratumumab-based treatment and the bortezomib-based regimen. The analysis used data from the MAIA and SWOG S0777 trials and incorporated local real-world data where available. Sensitivity analyses were performed to evaluate the robustness of the findings, and a risk analysis was conducted to analyze various payer strategies in terms of their payer strategy and uncertainty burden (P-SUB), which account for the decision uncertainty and the additional cost of choosing a suboptimal intervention.ResultsThe incremental cost-effectiveness ratio (ICER) for daratumumab, lenalidomide, and dexamethasone (DRd) compared with bortezomib, lenalidomide, and dexamethasone (VRd) was US $90,364 per QALY gained. The results were sensitive to variations in survival for DRd, postprogression treatment costs, cost of hospice care, and hazard ratio for progression-free survival. The scenarios explored indicated that structural assumptions, such as the time horizon of the analysis, significantly influenced the results due to uncertainties arising from immature trial data and treatment efficacy over time. Among the various payer strategies compared, an upfront price discount for daratumumab emerged as the best approach with the lowest P-SUB at US $14,708.ConclusionIn conclusion, this study finds that daratumumab as a first-line treatment for myeloma exceeds the cost-effectiveness threshold considered in this evaluation. An upfront price reduction is the recommended strategy to manage uncertainties and mitigate financial risks. These findings highlight the importance of targeted payer strategies to address specific types and sources of uncertainty.