Cost-Effectiveness Analysis of Triplet Regimens in Newly Diagnosed MM

Daratumumab- and bortezomib-based triplet regimens are not cost-effective compared with a regimen of lenalidomide and dexamethasone (Rd) among transplant-ineligible patients with newly diagnosed multiple myeloma (MM), according to an analysis published in the Journal of Managed Care + Specialty Pharmacy.

In this study, the researchers compared the cost-effectiveness of three regimens for MM: Rd alone, daratumumab plus Rd (DRd), or bortezomib and Rd (VRd).

“Daratumumab, a CD38-targeted, human IgG1k monoclonal antibody, and bortezomib, a proteasome inhibitor, are both approved as regimens for transplant-ineligible relapsed/refractory MM. There have been cost-effectiveness analyses for daratumumab and bortezomib use in relapsed/refractory MM, but there are limited data regarding cost-effectiveness for daratumumab or bortezomib use in newly diagnosed MM patients who are ineligible for stem cell transplantation,” the authors wrote.

The investigators developed a two-state Markov model with a U.S. healthcare system perspective and lifetime time horizon. To calculate transition probabilities, they utilized the latest progression-free survival data from MAIA and SWOG S0777, two phase 3 randomized controlled trials. Costs were calculated in 2019 U.S. dollars (discounted by 3%), via national data sources. Weighted utility decrements were applied for adverse events. The researchers defined cost-effectiveness at a willingness to pay (WTP) threshold of $150,000 per progression-free quality-adjusted life-year ($/PFQALY).

Average overall costs were $329,867 for Rd standard therapy, $385,434 for VRd, and $626,900 for DRd. Estimated PFQALYs were 1.24 for Rd, 1.35 for VRd, and 1.52 for DRd.

“The cost of DRd triple therapy was nearly 90% higher than Rd standard therapy and almost 62% more expensive than VRd triple therapy,” the authors commented.

At the $150,000 per PFQALY WTP threshold, neither triplet regimen was found to be cost-effective relative to standard therapy. The incremental cost-effectiveness ratio (ICER) for VRd compared with Rd was $530,256 per PFQALY, and $1,060,832 per PFQALY for DRd versus Rd. The ICER for DRd versus VRd was $1,396,318 per PFQALY. These data were “similar to previous [cost-effectiveness analysis] findings that looked at DRd vs. Rd in patients with relapsed/refractory MM,” authors noted.

Notably, the authors found that “the 3.5 mg vial size for bortezomib is higher than the average dose prescribed, leading to 36.9% of the dose being wasted for a person with a body surface area of 1.7m2. This amount of wastage was included in our model and was a factor leading to the high ICER for VRd.”

According to a probabilistic sensitivity analysis, at a WTP threshold of $550,000, VRd would be cost-effective for 40% of iterations. DRd was not found to be cost-effective compared with VRd at any WTP threshold up to $800,000.

“Neither DRd nor VRd triple therapy were found to be cost-effective vs. Rd,” the authors summarized. “Further cost-effectiveness analyses that include overall survival data for daratumumab and bortezomib triple therapies are needed to demonstrate an ICER in QALYs”