Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
The clinical evidence from the IMROZ trial indicates a moderate benefit of isatuximab in combination with bortezomib, lenalidomide, and dexamethasone over the comparator bortezomib, lenalidomide, and dexamethasone, with a hazard ratio of 0.596 for progression-free survival. However, the overall survival data is not statistically significant, indicating that while there is some evidence of benefit, it is not compelling enough to warrant a higher rating.
Cost effectiveness
The cost-effectiveness estimates for isatuximab are within the acceptable range that NICE considers for NHS resources, specifically towards the lower end of £20,000 to £30,000 per QALY gained. This suggests that the therapy is likely to be cost-effective given the benefits it provides.
Quality of life
The document indicates that the treatment may have a positive impact on quality of life, but there is insufficient robust data on HRQoL outcomes specifically associated with isatuximab. The committee noted that the utility values used in the economic model were derived from older studies and may not reflect current treatment pathways, leading to uncertainty about the actual HRQoL benefits.
Supporting Domains
Safety and Adverse Effects
The safety profile of isatuximab is reported to be very good, with mostly mild to moderate adverse events. The committee noted that the adverse events associated with isatuximab are manageable and comparable to existing therapies, indicating a favorable safety profile.
Comparator Selection
While the primary comparator, daratumumab plus lenalidomide and dexamethasone, is relevant, the lack of direct head-to-head trials raises concerns. The evidence relies on indirect comparisons, which introduces uncertainty regarding the robustness of the findings.
Patient Population and Subgroups
The IMROZ trial population is generally representative of the intended patient population in the NHS, although it was noted that the average age was younger than typical NHS patients. The committee concluded that the trial results are likely generalizable to the NHS setting.
Care Pathway Integration
Isatuximab can be integrated into existing treatment pathways with minor adjustments. The committee noted that the treatment fits well within the current standard of care for patients who are ineligible for stem cell transplant, requiring no significant changes to infrastructure.
Resource Use and Cost Implications
The budget impact of isatuximab is manageable, and the economic model indicates that the resource use aligns with the expected benefits. The committee concluded that the treatment is likely to be resource-efficient within the NHS context.
Evidence Quality and Robustness
The evidence base is supported by a Phase 3 RCT (IMROZ) with a reasonable sample size and follow-up duration. However, there are some concerns regarding the maturity of the data and the reliance on indirect comparisons, which introduces some uncertainty.
Uncertainty, Sensitivity, and Broader Impacts
There are notable uncertainties regarding the overall survival benefit and the robustness of the economic model due to the reliance on indirect comparisons and assumptions made in the analysis. The committee expressed concerns about the implications of these uncertainties on the decision-making process.
