On 14 June 2017, the NICE released a technology appraisal guidance [TA446] on brentuximab vedotin for treating CD30-positive Hodgkin lymphoma. Next recommendations apply:
1.1 Brentuximab vedotin is recommended as an option for treating CD30‑positive Hodgkin lymphoma in adults, only if:
- they have relapsed or refractory disease after autologous stem cell transplant and
- the company provides brentuximab vedotin at the price agreed with NHS England in the commercial access agreement.
1.2 Brentuximab vedotin is recommended for use within the Cancer Drugs Fund as an option for treating CD30‑positive Hodgkin lymphoma in adults, only if:
- they have relapsed or refractory disease after at least 2 previous therapies and
- they cannot have autologous stem cell transplant or multi-agent chemotherapy and
- the conditions of the managed access agreement are followed.
These recommendations are not intended to affect treatment with brentuximab vedotin that was started in the NHS before this guidance was published. Adults having treatment outside these recommendations may continue without change to the funding arrangements in place for them before this guidance was published, until they and their NHS clinician consider it appropriate to stop.
Brentuximab vedotin (Adcetris, Takeda UK) is an antibody–drug conjugate comprising an anti-CD30 monoclonal antibody attached by an enzyme-cleavable linker to a potent chemotherapeutic agent, monomethyl auristatin E (MMAE). The antibody–drug conjugate allows for the selective targeting of CD30-expressing cancer cells.
For populations 1 and 3, the company's submission mostly included retrospective, non-randomised evidence. The appraisal committee recognised that the available evidence was limited.
For population 2, the company's submission consisted of a randomised controlled trial (AETHERA). The appraisal committee considered this to be compromised to fit the data to the relevant high-risk group.
The committee noted that AETHERA included patients with Hodgkin lymphoma at risk of having residual disease after autologous stem cell transplant defined as those who have 1 risk factor. This definition was broader than that on which brentuximab vedotin's regulatory approval was based and the definition in the final NICE scope. To identify the high-risk group reflecting clinical practice in England, the company redefined high-risk patient criteria and identified a subgroup of patients which were accepted by committee (that is, people with a positive PET scan result before autologous stem cell transplant, plus at least 1 more risk factor).
The appraisal committee heard from the clinical experts that it was not routine practice in England to refer people for transplant who are at increased risk of disease relapse or progression, but it accepted that this population could be clinically relevant in the future.
The appraisal committee agreed that the clinical evidence base for all 3 populations was associated with uncertainty. There are no clinically relevant subgroups for which there is evidence of differential effectiveness.
For population 1, the overall response rate by independent review (primary outcome) was 75%.
For population 2, the median progression-free survival assessed by independent review (primary outcome) was 42.9 months for brentuximab vedotin and 24.1 months for placebo.
For population 3, the overall response rate (pooled dataset) investigator assessed was 50%. The overall response rates from C25007 and the UK observational dataset were 48% and 51% respectively.
The most common adverse events are nervous system disorders, including peripheral neuropathy, dizziness, and demyelinating polyneuropathy.
The recommended dose is 1.8 mg/kg administered by intravenous infusion over 30 minutes every 3 weeks.
The price of brentuximab vedotin is 2,500 GBP for a 50‑mg vial (excluding VAT; British national formulary June 2017).
The pricing arrangement considered during guidance development was one in which Takeda had agreed a patient access scheme with the Department of Health. This scheme would have provided a simple discount to the list price of brentuximab vedotin with the discount applied at the point of purchase or invoice. The Department of Health considered that this patient access scheme would not constitute an excessive administrative burden on the NHS. The commercial access agreement between the company and NHS England incorporates this same simple discount applied at the point of purchase or invoice of all brentuximab vedotin but also includes additional and separate commercial arrangements that apply only to the population in the Cancer Drugs Fund. The financial terms of the agreement are commercial in confidence.