OBJECTIVES: Although in the last decade many novel treatments were introduced for elderly non-transplant eligible (NTE) multiple myeloma (MM) patients, there is limited evidence on their relative cost-effectiveness. More importantly, there is no evidence on the outcomes of sequences of novel treatments. We investigated costs, effects and cost-effectiveness of novel treatment sequences in NTE MM patients.

METHODS: We adapted a patient-level simulation model including three lines of treatment, for elderly MM patients. The base-case sequence was modelled using real-world data on costs and effects from the Dutch PHAROS registry. For each novel treatment, we applied the Hazard Ratio for progression-free survival to the base-case treatment using results from two network meta-analyses (one for newly diagnosed NTE MM and one for relapsed/refractory MM). Finally, we estimated costs, effects, and cost-effectiveness for sixteen sequences reflecting current and future practice.

RESULTS: The base-case sequence (MPT-BorDex-LenDex) resulted in 3.1 Life-Years, 2.3 quality adjusted life-years (QALYs) and €107,985 (annual costs: €35,068). Two sequences that reflect current clinical practice (VMP-LenDex-PomDex and VMP-Lendex-CarDex) had reasonably comparable outcomes (4.1 [3.0] and 4.1 [3.1] Life-Years [QALYs], €241,560 and €275,371, respectively). The most effective future sequence (DVMP-CarLenDex-PanoBorDex; 5.9 [4.3] Life-Years [QALYs]) also yielded the highest costs (total €758,088 and annual €128,959). Another sequence (VMP-DaraLenDex-PanoBorDex) had similar effects (5.8 [4.3] Life-Years [QALYs]) but lower costs (total €572,417 and annual €99,287). Incremental cost-effectiveness ratios (ICERs) of sequences reflecting future practice compared to current practice ranged from €207,964 per QALY (VMP-CarLenDex-PomDex) up to €1,239,493 per QALY (VMP-CarDex-EloLenDex).

CONCLUSIONS: Combining internally valid trial evidence with generalizable real-world data facilitates valuable insights into effects, costs, and cost-effectiveness of novel treatments. All sequences including novel treatments in NTE MM yield better outcomes, but these benefits come, however, at much higher costs with ICERs above current willingness-to-pay thresholds.