Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
The evidence indicates that talquetamab has comparable efficacy to teclistamab, meeting non-inferiority but lacking clear superiority. The overall response rate was 69.5%, but median overall survival was not estimable, and median progression-free survival was only 11.2 months. The committee noted significant uncertainty in the indirect treatment comparison results, particularly regarding overall survival, which suggests that while talquetamab is effective, it does not demonstrate a clear therapeutic advance over existing treatments.
Cost effectiveness
The cost-effectiveness estimates for talquetamab fall within the acceptable range for NHS resources, with an ICER around £20,000 to £30,000 per QALY gained. The committee concluded that the cost-effectiveness estimates are defensible, although there remains some uncertainty regarding the overall survival benefit and the impact of COVID-19 on the clinical evidence.
Quality of life
The evidence suggests that talquetamab may improve quality of life, particularly due to its lower incidence of severe infections compared to teclistamab. Patient experts indicated that side effects, such as altered taste, are manageable and do not significantly detract from overall quality of life. However, the evidence is primarily based on clinical trial data, which may not fully capture real-world HRQoL impacts.
Supporting Domains
Safety and Adverse Effects
Talquetamab has a very good safety profile, with mostly mild to moderate adverse events reported. The committee noted that there were fewer severe infections compared to teclistamab, which supports its favorable safety profile. However, some concerns remain regarding the management of side effects, particularly altered taste and weight loss.
Comparator Selection
The evaluation compared talquetamab with teclistamab, which is a relevant and appropriate comparator for relapsed and refractory multiple myeloma. The committee acknowledged that teclistamab is commonly used in clinical practice, making it a suitable choice for comparison. However, the evolving treatment landscape may introduce some limitations in the comparators used.
Patient Population and Subgroups
The trial population for talquetamab is representative of the intended patient population, specifically those with relapsed and refractory multiple myeloma who have undergone multiple prior treatments. The committee noted that the majority of patients in clinical practice would align with the trial population, although some subgroup analyses could be more comprehensive.
Care Pathway Integration
Talquetamab can be integrated into existing care pathways with minor adjustments, as it does not require significant changes to current treatment protocols. The committee noted that the treatment regimen is manageable within the current healthcare system, which supports its adoption.
Resource Use and Cost Implications
The resource implications of talquetamab are manageable, with the potential for cost savings due to its favorable safety profile and reduced need for additional treatments. The committee concluded that the budget impact is justifiable given the expected benefits, although there are concerns about the overall affordability at scale.
Evidence Quality and Robustness
The evidence base for talquetamab includes data from ongoing phase 1 and 2 trials, which provides some robustness. However, the reliance on indirect treatment comparisons introduces uncertainty, particularly regarding overall survival estimates. The committee noted that while the evidence is generally credible, there are gaps that need to be addressed.
Uncertainty, Sensitivity, and Broader Impacts
There is considerable uncertainty surrounding the overall survival benefit of talquetamab compared to teclistamab, particularly due to the impact of COVID-19 on trial outcomes and the variability in treatment responses. The committee acknowledged these uncertainties but noted that real-world evidence may help mitigate some concerns.
