The Authors Respond

We are glad to have the opportunity to respond to the concerns noted in the previous letter from Medhekar et al. First, we must mention that the purpose of our study, as stated in our published article,¹ was to estimate the 1-year direct costs of triplet regimens used for the treatment of patients with previously treated multiple myeloma (MM). This warrants emphasizing, since the economic value of daratumumab-based triplet regimens for relapsed/refractory multiple myeloma (R/R MM) has been demonstrated previously,² so it was not the focus of our study. We agree that determination of value is important, but it is also important to ensure that budget is allocated to allow access to effective treatments.

In claiming overall survival (OS) superiority of carfilzomib regimens per the ASPIRE and ENDEAVOR trials,^3,4 Medhekar et al. ignore that the OS analyses for daratumumab regimens in the CASTOR or POLLUX trials have yet to be completed^5,6: insufficient deaths have occurred to date to trigger the a priori defined threshold. Medhekar et al. also do not acknowledge that clinically meaningful quality of life (QoL) improvement with carfilzomib + lenalidomide + dexamethasone (KRd) was lost at 18 weeks or that there was sustained QoL from cycle 3 and beyond with daratumumab + lenalidomide + dexamethasone (DRd).^7,8

We disagree with Medhekar et al. that our analysis penalizes regimens with longer progression-free survival (PFS). Whether PFS or OS, survival is a major clinical objective, but treating longer also costs more. Interestingly, Medhekar et al. did not mention that DRd had the greatest 1-year PFS, but KRd was the most costly option. Longer time horizons to accommodate decreases in dosing frequency might be helpful.⁹ However, payers plan budgets based on annual case-mix estimates, not patient trajectories.

Treatment may be discontinued for many reasons; however, progression was the main reason for discontinuation in the trials. Data for other causes were inconsistent. Medhekar et al. stated that we assumed only progression to be the marker of treatment duration. To the contrary, duration was either progression or the U.S. Food and Drug Administration (FDA) approved duration, whichever came first. Regarding heterogeneity, Medhekar et al. overlooked our rationale for the included regimens: all regimens were FDA-approved and equally recommended by the National Comprehensive Cancer Network MM guidelines for previously treated patients.¹⁰

A number of questionable challenges to our cost estimation methodology in Medhekar et al.’s letter must be noted. Absent real-world data, subsequent therapy costs beyond 1 year were calculated conservatively using established methods.¹¹ Hospitalization costs (inpatient/outpatient) were considered as part of managing adverse events grade ≥ 3 using literature. Other hospitalizations were excluded because data for all comparators were not available.

The claim that we underreported daratumumab administrations and thus underestimated the cost of daratumumab + bortezomib + dexamethasone (DVd) is not accurate, as there were no modeling errors—3 administrations of daratumumab were considered in each of the first 3 cycles. Table 1 highlights the values presented in the study and demonstrates that the modeled DVd drug acquisition costs of $150,192 are consistent with the label. Since these values are present in the study, had Medhekar et al. attempted to calculate the values, it would have been apparent that costs were not underestimated.

TABLE 1.

Key Values

	Values	Location in Published Study 1
Monthly DVd drug acquisition costs per patient	$12,516	Table 3
Yearly DVd drug acquisition cost per patient	$150,192	Calculated from Table 3 (12 × 12,516)
Cost cycle A (DVd)	$26,311	Table 1
Cost cycle B (DVd)	$13,054	Table 1
Cost cycle C (DVd)	$6,628	Table 1
Length of cycle A (DVd)	21 days	Table 1
Length of cycle B (DVd)	21 days	Table 1
Length of cycle C (DVd)	28 days	Table 1
Patients on DVd at 12 months	57.60%	Table 1

Note: Multiplying the cost of cycle a, b, and c, by 3, 5, and 7 (the number of times each cycle type occurs over a 1-year time horizon) yields $190,599. Application of the half-cycle corrected 1-year PFS estimate ($190,599 × [1 + 0.576) ÷ 2]) yields $150,192.

DVd = daratumumab + bortezomib + dexamethasone; PFS = progression-free survival.

From the title and throughout the text, our study is specified as a cost analysis—a perspective and approach that seemed to disconcert Medhekar et al. Their presumptive statements and categorical positions only strengthen our confidence in our study and resolve to support payers with objective evidence to support budgetary planning.