A cost-effectiveness analysis of JAK inhibitor therapy versus allogeneic stem cell transplantation in myelofibrosis.

Abstract

e18606 Background: Optimal management of myelofibrosis (MF) requires balancing the long-term overall survival benefits of allogeneic stem cell transplantation (allo-SCT) against risks associated with allo-SCT including infection, bleeding, graft-versus-host disease (GVHD), and other morbidities. JAK inhibitor therapy offers effective spleen volume reduction and symptom improvement yet lacks overt disease-modifying effect. Given limited evidence to guide this complex decision-making, we assessed the cost-effectiveness of JAK inhibitor therapy versus allo-SCT for 50-year-old patients with higher risk MF who are eligible for transplantation. Methods: We constructed a decision analytic model with a 5-year time horizon. We derived transplant outcomes, chronic GVHD occurrence and duration, non-relapse mortality, JAK inhibitor response and progression, and secondary AML transformation from published clinical trials and large cohort studies. The probability of remaining on chronic GVHD treatment beyond 2 years was modeled as a range to capture the uncertainty in prolonged treatment. Costs (2025$) and utilities used to calculate quality-adjusted life-years (QALYs) were obtained from the literature. We assumed all allo-SCT eligible patients have a matched sibling donor. We evaluated two strategies: upfront allo-SCT versus sequential JAK inhibitor therapy (ruxolitinib -> fedratinib -> momelotinib). Outcomes included life-years, QALYs, total costs, all discounted at 3% annually. Incremental cost-effectiveness ratios (ICERs) were calculated as the difference in total costs divided by the difference in QALYs and compared with a willingness-to-pay (WTP) threshold of $150,000. Results: Upfront allo-SCT incurred a total cost of $681,583 – $733,676 (higher cost corresponding to the upper limit of the probability of remaining on chronic GVHD treatment) and yielded 2.70 – 2.72 QALYs. Upfront JAK inhibitor therapy incurred a total cost of $889,009 and yielded 2.97 QALYs. ICER was $577,807 – 809,880, exceeding the WTP threshold. Results were sensitive to variation in chronic GVHD incidence and duration and JAK inhibitor drug costs. Sensitivity analysis showed that if a novel hypothetical medical therapy reduced the risk of transformation, medical therapy could become cost-effective. Conclusions: Our analysis demonstrates that allo-SCT and JAK inhibitor therapy can provide comparable health outcomes over a 5-years horizon for 50-year-old, transplant-eligible, higher risk MF patients with matched sibling donors. Differences in cost-effectiveness were largely driven by drug cost; at current prices, sequential JAK inhibitor therapy may therefore not be cost-effective. More data are needed to define outcomes after multiple JAK inhibitor failures. Additionally, future therapies that reduce transformation risk could shift the comparative value of medical therapy.