Cost-effectiveness of Novel Treatment Sequences for Transplant-Ineligible Patients With Multiple Myeloma

IMPORTANCE: Although the number of treatments for elderly patients with non–transplant-eligible (NTE) multiple myeloma (MM) has increased substantially, evidence is lacking on the clinical effectiveness and cost-effectiveness of novel treatment sequences. OBJECTIVE: To determine the optimal sequence of treatment for patients with NTE MM from the perspective of the patient, physician, and society. DESIGN, SETTING, AND PARTICIPANTS: Using data from a Dutch observational registry, this economic evaluation combined evidence from network meta-analyses in a patient-level simulation model and modeled time-to-event and types of events from a hospital perspective with a lifetime horizon. Data analysis was performed from June 2019 to September 2020. INTERVENTIONS: Thirty treatment sequences, including up to 3 lines of therapy, were compared with bortezomib-melphalan-prednisone (VMP)–lenalidomide-dexamethasone (LenDex)–pomalidomide-dexamethasone (PomDex). MAIN OUTCOMES AND MEASURES: The primary outcomes of the model were overall survival (OS), quality-adjusted life-years (QALYs), costs, and cost-effectiveness. RESULTS: Sequences starting with daratumumab-VMP (second line: carfilzomib-lenalidomide-dexamethasone or elotuzumab-lenalidomide-dexamethasone) or bortezomib-melphalan-prednisone-thalidomide-maintenance bortezomib-thalidomide (VMPT-VT) (second line: daratumumab-lenalidomide-dexamethasone) had the largest expected OS (7.5 years), which is 3.5 additional life-years compared with VMP-LenDex-PomDex. Total costs per patient for these sequences ranged between $786 024 and $1 085 794. The sequence VMPT-VT-carfilzomib-lenalidomide-dexamethasone–panobinostat-bortezomib-dexamethasone had the most favorable cost-effectiveness ratio ($98 585 per life-year gained and $132 707 per QALY gained vs VMP-LenDex-PomDex). CONCLUSIONS AND RELEVANCE: These findings suggest that sequences including novel treatments were highly effective, but the cost-effectiveness ratios were above currently accepted willingness-to-pay thresholds. Treating MM with novel agents necessitates either a large increase in budget or a substantial reduction of drug costs by price negotiations, and these findings can support these reimbursement decisions and price negotiations.