Transplant-ineligible patients with multiple myeloma (MM) have more treatment options today than in the past, but researchers are still looking for a successful treatment or series of treatments that can prolong patients’ lives without breaking the bank. Several novel treatment sequences hold a great deal of clinical promise, but their costs still exceed currently accepted willingness-to-pay thresholds, according to a recent study published in JAMA Network Open.

A team of researchers from the Netherlands created a patient-level simulation model and entered data on elderly patients with non-transplant-eligible (NTE) MM from the Dutch observational registry PHAROS. Their goal was to provide evidence about the effectiveness of treatment sequences in the context of cost and cost effectiveness.  They compared 30 treatment sequences with a baseline sequence.

The researchers identified 2 treatment sequences that were the most clinically effective, in terms of the largest expected overall survival rate (up to 7.5 years, an increase of 3.5 years over some other treatments):

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  • Sequences starting with DaraVMP (daratumumab plus bortezomib, melphalan, and prednisone) as the first-line treatment, followed with CarLenDex (carfilzomib-lenalidomide-dexamethasone) or EloLenDex (elotuzumab-lenalidomide-dexamethasone) for the second-line treatment;
  • Sequences starting with VMPT-VT (bortezomib-melphalan-prednisone-thalidomide followed by bortezomib-thalidomide maintenance) for the first-line treatment, followed by DaraLenDex (daratumumab, with lenalidomide-dexamethasone) for the second-line treatment.

But patients and providers must take cost into account. The researchers found that these effective treatment sequences varied in cost from $786,024 to $1,085,794. On average, that could increase the treatment cost as much as $800,000 per patient, when compared with the cost of VMP-LenDex-PomDex (bortezomib-melphalan-prednisone, lenalidomide-dexamethasone, pomalidomide-dexamethasone), which was used as the base treatment for comparison in this study.

However, the most effective treatment sequences weren’t the most expensive, either. That distinction of the highest total cost belonged to DaraLenDex-CarDex-PomBorDex, which had a total cost of nearly $1.14 million and a lower mean overall survival of 5.4 years.

The researchers noted that the costs exceeded reimbursement thresholds in the Netherlands and the United Kingdom. “The increased costs for treatment MM with the novel agents necessitate either a large increase in budget or a substantial reduction of drug cost imposed by price negotiations,” they concluded.

Disclosure: Multiple authors declared affiliations with and received funding from the pharmaceutical industry. Please refer to the original abstract for a full list of disclosures.


Blommestein HM, Franken MG, van Beurden-Tan CHY, et al. Cost effectiveness of novel treatment sequences for transplant-ineligible patients with multiple myeloma. JAMA Netw Open. 2021;4(3):e3213497. doi:10.1001/jamanetworkopen.2021.3497