Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
Pembrolizumab shows moderate benefit over the standard of care, with evidence from the KEYNOTE-204 trial indicating longer median progression-free survival compared to brentuximab vedotin (54.7 weeks vs. 35.7 weeks). However, the overall survival data is currently immature, which limits the strength of the evidence.
Cost effectiveness
Pembrolizumab is considered cost-effective, with an ICER under £20,000 per QALY gained in the relevant populations. The committee concluded that it represents a good use of Healthcare resources, especially when considering the potential overall survival benefit.
Quality of life
The evidence suggests that pembrolizumab may improve quality of life compared to brentuximab vedotin, particularly due to lower rates of severe side effects. However, the data on health-related quality of life is uncertain and based on limited follow-up.
Supporting Domains
Safety and Adverse Effects
Pembrolizumab has a very good safety profile, with mostly mild or moderate adverse events reported. The committee noted that it is more tolerable than brentuximab vedotin, which has higher rates of severe side effects.
Comparator Selection
The treatment was compared against brentuximab vedotin, which is an appropriate comparator for the patient population. The evidence from the KEYNOTE-204 trial supports this choice, although the marketing authorisation is narrower than the trial population.
Patient Population and Subgroups
The trial population is generally representative of the intended patient population, with subgroup analyses indicating that the results are applicable to those who have had at least 2 previous treatments.
Care Pathway Integration
Pembrolizumab can be integrated into existing treatment pathways with minor adjustments. It is positioned as a third-line treatment option, which fits within current clinical practice for relapsed or refractory classical Hodgkin lymphoma.
Resource Use and Cost Implications
The budget impact is manageable, and the treatment is expected to be resource-efficient, particularly given the cost-effectiveness findings. The commercial arrangement also provides a discount, further supporting its affordability.
Evidence Quality and Robustness
The evidence is based on a well-conducted Phase III trial (KEYNOTE-204) with low bias risk. However, the lack of mature overall survival data introduces some uncertainty.
Uncertainty, Sensitivity, and Broader Impacts
While there are uncertainties regarding overall survival estimates, the context of unmet need and the potential benefits of pembrolizumab support its use. The committee noted that the treatment addresses a significant gap in care for this patient population.
