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Although, MM remains the most common indication for ASCT in the US, a controversy exists about the timing of ASCT. Since early ASCT (eASCT) versus delayed ASCT (dASCT) results in similar progression free survival (PFS) and overall survival (OS), economic assessment of both strategies would help in MM treatment paradigm. A decision tree was developed to compare the outcomes of ASCT in newly diagnosed transplant eligible MM patients after chemotherapy with lenalidomide. The survival data was obtained from our published data on eASCT versus dASCT in MM patients who underwent initial therapy with dexamethasone + immunomodulatory agents (IMiDs). The initial decision node on the decision tree model was dichotomized based on the cutoff of 12 months (m) for eASCT versus dASCT. The probabilities of events during the length of follow up (60m) period which formed our base case (BC) are: (a) eASCT cohort: IMiD for median of 6m > ASCT > median 30m to relapse (and drug free interval) > median therapy of 24m for relapsed MM; (b) dASCT cohort: Median initial therapy for 36m > ASCT > median 24m to relapse (and drug free interval).
The cost data for MM ASCT was obtained from published data of direct hospital costs obtained from Nationwide Inpatient Sample and were converted to Medicare cost-to-charge ratio. Chemotherapy cost consisted of average wholesale prices AWP (2008), costs of medical oncology visits, and cost of managing adverse events. TreeAge Pro 2012 software was used to perform a static decision analysis.
The outcomes were expressed in the units of health utility values obtained from phase III HOVON trial which measured quality of life (QoL) using EORTC QLQ-C30 & EuroQoL-5D scales. Using a Consumer Price Index (CPI), the costs were converted into 2012 US$. The expected cost of providing treatment to newly diagnosed MM patients for a period of 5 yrs when they undergo eASCT after induction with IMiD was $211,869 ($52,454 less than the dASCT) and had an expected benefit of 2.06 QALYs following treatment (0.19 QALYs more than dASCT) implying that eASCT is preferred over (dominates) dASCT. Tornado diagram and one-way sensitivity analysis results indicated that eASCT showed dominance even if the probability of OS was lowered to 52.1% (from BC of 65%), or the probability of ORR was lowered to ≥ 75.8% (from BC of 92%), or the probability of 1 year TRM was increased to 11.5% (from BC of 2%).
In absence of a survival benefit, the cost savings of early ASCT as measured by ICER would favor this approach, and it would help clinicians, patients, policy makers and third party payers in decision making. Future prospective studies in MM ASCT should incorporate economic and QOL components in the analysis and also focus on the added cost of post-ASCT maintenance therapies.
