Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
Acalabrutinib shows moderate benefit over current care, particularly in increasing progression-free survival compared to chlorambucil plus obinutuzumab. However, the overall survival benefit remains uncertain due to immature data, which limits the strength of the evidence.
Cost effectiveness
The cost-effectiveness analysis indicates that acalabrutinib is likely to be cost-saving compared to ibrutinib for high-risk patients and remains within acceptable thresholds for untreated CLL when FCR or BR is unsuitable.
Quality of life
The evidence indicates that acalabrutinib is generally well tolerated and associated with fewer adverse effects compared to current treatments, suggesting a moderate improvement in quality of life for patients with CLL.
Supporting Domains
Safety and Adverse Effects
Acalabrutinib has a very good tolerability profile with fewer adverse effects compared to existing treatments, indicating a strong safety profile.
Comparator Selection
The company did not present direct comparisons with all relevant comparators, particularly venetoclax plus rituximab, which limits the robustness of the evidence.
Patient Population and Subgroups
The trial populations are broadly representative of the intended patient population, although there are some gaps in subgroup analyses for those suitable for FCR or BR.
Care Pathway Integration
Acalabrutinib can be integrated into existing treatment pathways with minor adjustments, as it offers a new option for patients who cannot tolerate current therapies.
Resource Use and Cost Implications
The budget impact is manageable, and the treatment is likely to be resource-efficient, particularly given the cost-saving potential compared to ibrutinib.
Evidence Quality and Robustness
The evidence is based on well-conducted RCTs, although there are some uncertainties regarding the indirect comparisons and the maturity of survival data.
Uncertainty, Sensitivity, and Broader Impacts
There are notable uncertainties regarding overall survival estimates and the distribution of subsequent treatments, which could impact the decision-making process.
