Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
The clinical trial evidence from the MAIA trial shows that daratumumab plus lenalidomide and dexamethasone significantly increases progression-free survival and overall survival compared to lenalidomide plus dexamethasone. Specifically, it reduces the risk of disease progression and death by 45% and 34%, respectively. However, the overall survival data is still considered relatively immature, which prevents a higher rating.
Cost effectiveness
The cost-effectiveness estimates for daratumumab plus lenalidomide and dexamethasone fall within the range that NICE considers acceptable for Healthcare resources. The committee noted that the ICERs were lower than the maximum acceptable threshold, indicating a strong economic value.
Quality of life
While the document indicates potential improvements in quality of life, particularly in terms of reduced anxiety and better overall well-being, the evidence is not robustly quantified with validated tools. The committee acknowledged possible uncaptured benefits related to HRQoL, but the lack of specific data limits the rating.
Supporting Domains
Safety and Adverse Effects
The safety profile of daratumumab plus lenalidomide and dexamethasone is reported as very good, with mostly mild or moderate adverse events. Serious adverse events are rare, supporting a favorable tolerability compared to existing therapies.
Comparator Selection
The treatment was compared against appropriate standard-of-care alternatives, primarily lenalidomide plus dexamethasone, which is the most widely used treatment option. The inclusion of bortezomib combination treatments as secondary comparators further strengthens the evidence.
Patient Population and Subgroups
The MAIA trial included a diverse population of adults with untreated multiple myeloma who are ineligible for autologous stem cell transplant, making the results broadly generalizable. However, some concerns about representativeness and subgroup analysis were noted.
Care Pathway Integration
The integration of daratumumab plus lenalidomide and dexamethasone into existing treatment pathways is expected to be manageable, with minor adjustments needed. The treatment aligns well with current clinical practices for multiple myeloma.
Resource Use and Cost Implications
The budget impact is considered manageable, with the treatment being resource-efficient. The committee noted that the overall resource implications are justifiable given the expected health outcomes.
Evidence Quality and Robustness
The evidence is primarily based on a robust Phase 3 trial (MAIA), although there are some methodological concerns and uncertainties regarding long-term outcomes. The overall quality of evidence is strong but not without limitations.
Uncertainty, Sensitivity, and Broader Impacts
There are notable uncertainties regarding the long-term effectiveness and generalizability of the results to Healthcare clinical practice. The committee expressed concerns about the assumptions made in the economic model, which could impact the decision-making process.
