Real-World Cost-Effectiveness of Sequential Ixazomib versus Daratumumab in Multiple Myeloma

Recently, the collaborative pharmacoeconomic research project involving Normin Health and leading clinical and health economic institutions across China, titled "Real-world cost-effectiveness of sequential therapy of in-class transition to ixazomib versus daratumumab for transplant-ineligible newly diagnosed multiple myeloma in China," was successfully published in the Journal of Comparative Effectiveness Research. As therapeutic options for multiple myeloma continue to expand, understanding their long-term clinical and economic impact is critical for healthcare decision-makers. Because no randomized clinical trial has compared these two treatment strategies head-to-head, this study demonstrates what real-world evidence (RWE) brings to cost-effectiveness modeling that clinical trials cannot.

Key Highlights of the Study:

RWE-Driven Modeling Framework: The study developed a lifetime discrete state-transition Markov cohort model from the Chinese healthcare system perspective. Rather than relying on trial-based assumptions, the model was parameterized almost entirely from real-world inputs synthesized across 280 observational studies, comparing sequential in-class transition to oral ixazomib (iCT IRd) against upfront daratumumab (DRd).

Major Findings:

The Discontinuation Factor (Where Trials Mislead): Model findings clearly illustrate that cost-effectiveness hinges heavily on treatment discontinuation and persistence—an area where clinical trials often mislead due to protocolized adherence management. In routine real-world practice, over 80% of transplant-ineligible patients discontinue daratumumab-based therapy within 15 months, whereas an all-oral continuous regimen offers superior convenience and sustained adherence for elderly or frail patients.

Dominant Health and Economic Value: In the base-case analysis, the sequential iCT IRd strategy generated an additional 0.580 QALYs (4.724 vs 4.144 QALYs) and 0.738 life years (5.914 vs 5.177 years), while reducing lifetime direct medical expenditures by $7,751 per patient ($89,274 vs $97,025) compared to upfront DRd, achieving clinical and economic dominance.

Substantial Front-Line Cost Reductions: Lifetime front-line treatment costs were markedly lower with iCT IRd ($46,963 vs $66,546, a net reduction of $19,583), driven by reduced drug acquisition costs (-$14,335) and lower outpatient administration and monitoring burden (-$4,080).

Strategic Whole-Course Sequencing: Health gains were strongly driven by treatment persistence and the strategic advantage of preserving anti-CD38 antibody regimens (DRd) for subsequent lines of therapy, unlocking long-term survival value across the disease continuum.

High Probabilistic Cost-Effectiveness: Probabilistic sensitivity analysis (5,000 Monte Carlo iterations) showed a 55.0% probability of outright dominance. At willingness-to-pay thresholds of 1×, 2×, and 3× China's 2025 GDP per capita per QALY, iCT IRd demonstrated 79.2%, 88.0%, and 91.3% probabilities of being cost-effective, respectively.

Clinical and Policy Implications:

Evaluating long-term real-world trajectories is essential for informed treatment planning and healthcare resource allocation. This study showcases how RWE bridges critical evidentiary gaps where direct trial data are absent, demonstrating that an all-oral sequential transition strategy (iCT IRd) offers a cost-effective, patient-centered option for transplant-ineligible ndMM patients in China while optimizing healthcare system affordability.

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