Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
The clinical evidence suggests that mosunetuzumab shows comparable efficacy to existing treatment options, with a complete response rate of 58% in the pivotal cohort compared to a historical control rate of 14%. However, the lack of a Phase 3 trial and direct comparisons with standard care limits the strength of this evidence, leading to a rating of B++.
Cost effectiveness
The cost-effectiveness estimates for mosunetuzumab are highly uncertain and do not represent a cost-effective use of Healthcare resources, with ICERs above £30,000 per QALY gained. This uncertainty and lack of cost-effectiveness justify a rating of C.
Quality of life
There is limited data on HRQoL improvements associated with mosunetuzumab. While clinical experts noted that it is well tolerated and not associated with lingering effects seen with chemotherapy, specific validated HRQoL measures were not reported, resulting in a rating of B+.
Supporting Domains
Safety and Adverse Effects
Mosunetuzumab has an acceptable safety profile, with the most common adverse event being cytokine release syndrome, which was mostly mild (grade 1 or 2). Clinical experts noted that it was well tolerated, leading to a rating of A.
Comparator Selection
The indirect treatment comparisons used rituximab plus lenalidomide and rituximab plus bendamustine as comparators, which are relevant but not ideal. The committee noted that the representativeness of these comparators is uncertain, leading to a rating of B++.
Patient Population and Subgroups
The study population is considered broadly representative of the intended patient population in UK clinical practice, with clinical experts confirming its relevance. This leads to a rating of A+.
Care Pathway Integration
Mosunetuzumab can be integrated into existing care pathways with manageable adjustments, as it can be administered in non-specialist centres with proper training. This results in a rating of A.
Resource Use and Cost Implications
The resource implications of mosunetuzumab are significant, with high treatment costs and uncertainty regarding its budget impact. This leads to a rating of B.
Evidence Quality and Robustness
The evidence base is primarily from a single-arm Phase 2 trial, which raises concerns about robustness and generalizability. The lack of Phase 3 data contributes to a rating of B++.
Uncertainty, Sensitivity, and Broader Impacts
There are significant uncertainties regarding the cost-effectiveness and clinical outcomes of mosunetuzumab, particularly due to the reliance on indirect comparisons and the immaturity of survival data. This leads to a rating of B+.
