Economic advantage of daratumumab, bortezomib, lenalidomide, and dexamethasone vs bortezomib, lenalidomide, and dexamethasone for transplant-ineligible or transplant-deferred newly diagnosed multiple myeloma: A cost-per-responder evaluation

BACKGROUND: In the phase III CEPHEUS trial, 8 cycles of daratumumab (D), bortezomib (V), lenalidomide (R), and dexamethasone (d) followed by monthly DRd were associated with a higher rate of minimal residual disease (MRD) negativity compared with VRd followed by Rd among patients with transplant-ineligible/transplant-deferred, newly diagnosed multiple myeloma. OBJECTIVE: To compare the health care costs of patients achieving and sustaining MRD negativity with first-line (1L) DVRd vs VRd. METHODS: Using CEPHEUS trial data, an economic model was developed from a US mixed-payer perspective (80% Medicare, 20% commercial) over a 60-month horizon. Model inputs included drug acquisition and administration costs for 1L and second-line (2L) therapies, medical care costs during 1L and 2L treatment, adverse event management costs, and next-generation sequencing MRD testing costs. Cost per patient negative for MRD was calculated based on the cost per patient treated and the cumulative proportion of patients achieving MRD negativity at 60 months after randomization. Cost per patient achieving sustained MRD negativity was estimated based on the proportion of patients with MRD-negative status on at least 2 occasions that were at least 12 months apart during the 60 months after randomization in CEPHEUS. Costs were reported in 2025 US dollars. RESULTS: At 60 months, the total costs per patient negative for MRD were $652,113 lower with DVRd vs VRd, driven by a higher proportion of patients achieving MRD-negative status (DVRd = 60.9%; VRd = 39.4%) and the lower 2L treatment costs per patient with MRD-negative status with DVRd vs VRd (DVRd = $186,371; VRd = $958,840), attributable to the lower proportion of patients progressing to 2L treatment (DVRd = 11.2%; VRd = 33.3%). The cost per patient achieving sustained MRD negativity was $1,964,539 lower with DVRd than VRd, driven by a higher proportion of patients achieving sustained MRD negativity (DVRd = 48.7%; VRd = 26.3%) and the $1,203,376 lower 2L treatment costs per patient in the DVRd cohort (DVRd = $233,060; VRd = $1,436,436). CONCLUSIONS: Among patients with transplant-ineligible or transplant-deferred newly diagnosed multiple myeloma, 1L treatment with DVRd was associated with lower costs per patient with MRD-negative status and per patient achieving sustained MRD negativity compared with treatment with VRd. These findings complement the superior clinical efficacy observed with 1L DVRd compared with VRd in the CEPHEUS trial by demonstrating the potential cost savings associated with DVRd.