Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
Daratumumab monotherapy shows moderate benefit over the standard of care (pomalidomide plus dexamethasone) in terms of overall survival, although the exact magnitude of this benefit remains uncertain. The evidence from the MMY2002 study and the SACT dataset indicates that daratumumab increases overall survival, but the lack of head-to-head trials limits the robustness of this conclusion.
Cost effectiveness
The cost-effectiveness estimates for daratumumab are within acceptable thresholds for Healthcare resources, with the most likely ICER being below £50,000 per QALY gained. Despite some uncertainty, the committee concluded that it represents a defensible economic value.
Quality of life
The evidence suggests that daratumumab is well tolerated and improves quality of life for patients, allowing them to receive further treatments. Patient experts reported significant improvements in their quality of life, indicating strong domain-specific gains.
Supporting Domains
Safety and Adverse Effects
Daratumumab has a favorable safety profile with mostly mild to moderate adverse events. The clinical expert and patient feedback indicate that it is well tolerated compared to other treatments, which supports its use in the treatment pathway.
Comparator Selection
The primary comparator, pomalidomide plus dexamethasone, is appropriate; however, the absence of head-to-head evidence and reliance on indirect comparisons through MAICs raises concerns about the robustness of the evidence.
Patient Population and Subgroups
The patient population in the clinical evidence is representative of those who would receive daratumumab in practice, with relevant subgroup analyses indicating that the treatment is applicable to a broad range of patients.
Care Pathway Integration
Daratumumab can be integrated into existing treatment pathways with minor adjustments. The treatment is compatible with current clinical practices, requiring no significant new infrastructure or training.
Resource Use and Cost Implications
The resource implications of daratumumab are manageable, with the potential for cost savings due to its effectiveness in extending life and improving quality of life, aligning with Healthcare budget considerations.
Evidence Quality and Robustness
The evidence base includes a phase-2 study and real-world data from the SACT dataset, which, while not ideal, provides a reasonable level of confidence in the findings despite some methodological limitations.
Uncertainty, Sensitivity, and Broader Impacts
There is significant uncertainty regarding the overall survival estimates and the effectiveness of daratumumab compared to pomalidomide plus dexamethasone. The committee acknowledged this uncertainty but noted that it could be addressed in future appraisals.
