Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
The clinical evidence for loncastuximab tesirine is derived from a single-arm Phase 2 trial (LOTIS-2) which reported a 48% overall response rate and a 25% complete remission rate. However, there was no direct comparison with standard treatments, leading to uncertainty about its relative effectiveness. Indirect comparisons suggest it may be as effective as polatuzumab plus BR but with considerable uncertainty, thus justifying a B++ rating.
Cost effectiveness
The cost-effectiveness estimates for loncastuximab tesirine compared to chemotherapy are likely below the acceptable threshold of £20,000 per QALY gained, making it marginally cost-effective. However, it is more expensive than polatuzumab plus BR, which affects its overall cost-effectiveness perception, justifying an A rating.
Quality of life
The document does not provide specific data on HRQoL improvements associated with loncastuximab tesirine. While it mentions the severe impact of DLBCL and HGBL on patients’ lives, the absence of robust HRQoL data leads to a B+ rating, indicating no demonstrated benefit over standard care.
Supporting Domains
Safety and Adverse Effects
Loncastuximab tesirine has been reported to have a good safety profile with manageable adverse effects. The committee noted that it was well-tolerated in trials, which supports a strong safety rating, though some adverse effects were acknowledged.
Comparator Selection
The comparators selected for the evaluation, including polatuzumab plus BR and chemotherapy, are relevant and reflect current treatment practices. The committee concluded that these comparators were appropriate despite the evolving treatment landscape.
Patient Population and Subgroups
The trial population included patients with relapsed or refractory DLBCL and HGBL, which is representative of the intended patient population. However, there are some limitations in subgroup analyses, but overall, the population is considered broadly generalizable.
Care Pathway Integration
Loncastuximab tesirine can be integrated into existing treatment pathways with minor adjustments, as it is administered as a single infusion. This ease of integration supports a strong rating.
Resource Use and Cost Implications
While the treatment is expected to have a manageable budget impact, the overall resource burden is notable due to its high cost compared to alternatives. This leads to a B++ rating, indicating some concerns about resource implications.
Evidence Quality and Robustness
The evidence base is primarily from a single Phase 2 trial with indirect comparisons, which introduces uncertainty and potential biases. While the trial was well-conducted, the lack of direct comparative evidence limits the robustness of the findings.
Uncertainty, Sensitivity, and Broader Impacts
There are significant uncertainties regarding the indirect comparisons and the assumptions made in the economic model. The committee noted these uncertainties but did not find them sufficient to block the recommendation, leading to a B+ rating.
