Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
The evidence from the ASPIRE trial shows that carfilzomib plus lenalidomide and dexamethasone significantly improves both progression-free survival (PFS) and overall survival (OS) compared to lenalidomide plus dexamethasone, with median PFS increasing from 16.6 months to 26.1 months and median OS from 40.4 months to 48.3 months. This indicates a clear clinical advantage, although the long-term durability of these benefits remains uncertain.
Cost effectiveness
The cost-effectiveness estimates for carfilzomib plus lenalidomide and dexamethasone are likely to be below £30,000 per QALY gained, which is within NICE’s acceptable range for Healthcare resources. The committee concluded that the most plausible ICERs are acceptable, although some caution is warranted due to potential overestimation of treatment benefits.
Quality of life
The ASPIRE trial utilized the EORTC QLQ-C30 questionnaire, which indicated a statistically significant difference in global health status scores between treatment arms. However, the committee noted that there were no significant differences in other HRQoL domains, suggesting moderate improvements in quality of life, primarily due to disease control rather than direct treatment benefits.
Supporting Domains
Safety and Adverse Effects
The safety profile of carfilzomib is considered very good, with mostly mild to moderate adverse events reported. Serious adverse events are rare, and the overall tolerability is comparable to existing therapies, supporting a favorable safety assessment.
Comparator Selection
The primary comparator used in the ASPIRE trial was lenalidomide plus dexamethasone, which is appropriate. However, the committee noted that daratumumab plus bortezomib and dexamethasone, a relevant comparator, could not be considered due to NICE’s position on the Cancer Drugs Fund, limiting the robustness of the comparative evidence.
Patient Population and Subgroups
The trial population is moderately representative, focusing on patients who have had only one previous treatment containing bortezomib. The committee acknowledged that the subgroup analyses were appropriate and reflected the current treatment pathway for multiple myeloma.
Care Pathway Integration
Carfilzomib can be integrated into existing treatment pathways with manageable adjustments. The committee noted that the treatment aligns well with current clinical practices, requiring no significant new infrastructure or training.
Resource Use and Cost Implications
The budget impact of carfilzomib is manageable, with the potential for cost savings due to its effectiveness in extending remission periods. The committee concluded that the resource implications are aligned with planning and do not raise significant concerns.
Evidence Quality and Robustness
The evidence base is strong, primarily derived from the ASPIRE trial, which is a well-designed RCT. While there are some methodological concerns, the overall quality of evidence is acceptable and supports the conclusions drawn.
Uncertainty, Sensitivity, and Broader Impacts
There is notable uncertainty regarding the long-term benefits of carfilzomib after treatment cessation, which could impact cost-effectiveness estimates. The committee recognized this uncertainty but noted that it is somewhat mitigated by the context of unmet need in multiple myeloma treatment.
