Authors' objectives: The Academic Technology Assessment Group (ATAG) reviewed a report by the manufacturer (Pfizer Japan Inc.) on the additional benefits and cost-effectiveness of elranatamab in patients with relapsed or refractory multiple myeloma. This report summarizes the ATAG review and reanalysis. The target population was patients with relapsed or refractory multiple myeloma who had received at least three prior therapies, including an immunomodulatory drug, a proteasome inhibitor, and an anti-CD38 monoclonal antibody, with no prior exposure to B-cell maturation antigen-directed therapies. The comparator was elotuzumab plus pomalidomide and dexamethasone (EPd). The manufacturer conducted a systematic review (SR) to assess the additional benefits of elranatamab in the target population and found no randomized controlled trials (RCTs) directly comparing elranatamab and EPd. Instead, the pivotal single-arm trial of elranatamab (MagnetisMM-3) and non-RCTs including EPd among physicianfs choice of treatment (PCT) were identified. The manufacturer regarded the target population in the observational study of PCT (LocoMMotion) as the population demonstrating the efficacy of EPd. The manufacturer conducted an unanchored matching-adjusted indirect comparison (MAIC) using individual patient data from the MagnetisMM-3 trial and aggregate data from the LocoMMotion study. Elranatamab significantly prolonged overall survival (OS) and progression-free survival (PFS) compared with EPd according to the results of this indirect comparison. The manufacturer concluded that elranatamab provides additional benefits compared with EPd. The ATAG independently conducted the SR. The ATAG identified an RCT comparing EPd and pomalidomide plus dexamethasone and observational EPd studies in addition to the MagnetisMM-3 trial. The ATAG noted concerns about substituting PCT outcomes for EPd efficacy because the comparator in the framework of analysis was EPd. However, the ATAG accepted the unanchored MAIC-based findings of the manufacturer and considered elranatamab as providing additional benefits compared with EPd for the target population given the limited and fragmented evidence available and the difficulty of conducting alternative reanalyses. Thus, the ATAG examined the analysis provided by the manufacturer as the cost-effectiveness analysis was appropriate. The manufacturer built a partitioned survival model with three health states?progression-free, progressed disease, and death ? using quality-adjusted life year (QALY) as the outcome and EPd as the comparator for the economic evaluation. EPd parameterization, including OS and PFS, relied on the LocoMMotion data. The ATAG conducted a reanalysis owing to the several challenges identified in the analysis by the manufacturer. First, the manufacturer estimated the time to discontinuation of elranatamab using the median treatment duration in the MagnetisMM-3 trial using a constant hazard model. However, this approach diverged from the observed treatment duration and was inconsistent with the PFS curve. The ATAG evaluated alternative parametric curves and selected a log-normal distribution based on a visual inspection of model fit, the Akaike information criterion, the Bayesian information criterion, and consistency with follow-up data from the MagnetisMM-3 trial. Second, the manufacturer did not consider intravenous immunoglobulin (IVIG) use, despite hypogammaglobulinemia being a clinically important adverse outcome of elranatamab therapy. The ATAG incorporated IVIG use through assuming that 43.1% of patients treated with elranatamab received IVIG, consistent with the MagnetisMM-3 trial results, and added the costs of IVIG. The reanalysis of the ATAG showed that elranatamab led to an incremental effectiveness of 1.77 QALYs and an incremental cost of JPY 11,352,276 compared with EPd, resulting in an incremental costeffectiveness ratio (ICER) of JPY 6,419,472 per QALY. In conclusion, for patients with relapsed or refractory multiple myeloma, the results by the ATAG suggested that the ICER for elranatamab compared to EPd was likely to belong to the interval between JPY 2 and 7.5 million per QALY from the perspective of public healthcare payer in Japan.

Project Status: Completed

URL for project: https://c2h.niph.go.jp/en/

Year Published: 2025

URL for published report: https://c2h.niph.go.jp/en/results/C2H2403.html

English language abstract: An English language summary is available

Publication Type: Not Assigned

Country: Japan

Organisation Name: Center for Outcomes Research and Economic Evaluation for Health

Contact Address: 2-3-6 Minami, Wako-shi, Saitama 351-0197 Japan

Contact Name: Takeru Shiroiwa

Contact Email: t.shiroiwa@gmail.com