Advice

The technology

The technology

AMBLor (AMLo Biosciences) is a prognostic risk stratification test for identifying low-risk non-ulcerated early-stage cutaneous melanoma in children and adults. This immunohistochemical assay uses 2 monoclonal antibodies that recognise the proteins AMBRA1 and loricrin in the epidermis covering the melanoma tumour. AMBRA1 is an autophagy protein that is involved in cell proliferation and differentiation and is a tumour suppressor. Loricrin is a marker of epidermal terminal differentiation. Melanomas with a lower risk of recurrence or spread retain the expression of AMBRA1 or loricrin, or both, in the tumoural epidermis. Tumours with higher risk lose the expression of both proteins.

AMBLor is used to qualitatively detect AMBRA1 and loricrin proteins by light microscopy in formalin-fixed paraffin-embedded sections of non-ulcerated primary cutaneous melanomas. It has been developed for use with the Ventana UltraView DAB immunohistochemistry (IHC) detection kit and Ventana BenchMark Ultra instrument. Positive and negative controls should be run with every test.

Innovations

The company claims that AMBLor uses a unique and patented immunohistochemical method and detection antibodies. It claims there is no other technology that can classify risk in non-ulcerated early-stage cutaneous melanoma.

Current care pathway

All pigmented skin lesions referred for assessment should be assessed using dermoscopy. Staging of melanoma is based on the American Joint Committee on Cancer (AJCC) cancer staging system. This considers the progression of the primary tumour and the spread of melanoma in the body. The initial staging of primary melanoma is based on the histopathological features of the tumour. The melanoma is staged as 0 to 2C based on factors such as thickness of the tumour and ulceration. A sentinel lymph node biopsy may also be done in stages 1B to 2C melanoma to detect secondary melanoma cells. If cancer cells are found in the sentinel nodes, the melanoma becomes stage 3. Stage 4 melanoma is when it has spread to distant parts of the body. Along with AJCC staging, other histopathological details may be used to assess risk of recurrence in melanoma by the multidisciplinary team.

Treating stages 1 to 2 melanoma involves excision to remove the melanoma and surrounding skin. After treatment, everyone is followed up in clinic for regular skin and lymph node examination. This aims to detect recurrence and other primary melanomas. Follow-up appointments are usually offered:

  • Stage 1A: 2 to 4 times during the first year after treatment.

  • Stages 1B to 2B: every 3 months for the first 3 years after treatment, then every 6 months for the next 2 years.

People would usually be discharged after completing these follow ups if no recurrence or new melanomas are found.

The following publications have been identified as relevant to this care pathway:

Population, setting and intended user

Around 1 in 36 men and 1 in 47 women in the UK will be diagnosed with melanoma skin cancer in their lifetime, with about 16,700 new cases each year. In 2018, around 64% of people with melanoma were diagnosed at stage 1 and 19% at stage 2.

AMBLor is intended for use in non-ulcerated stage 1, 2A or 2B melanoma. It is only indicated for cutaneous melanoma that has been removed by excisional biopsy. It is not indicated for frozen biopsies and should not be used with:

  • ulcerated stage 1 or 2 cutaneous melanomas

  • stage 3 or above melanoma

  • mucosal, acral, or uveal melanomas

  • punch or shave biopsies

  • melanoma that is in a psoriatic or eczemic lesion.

The AMBLor reagent kit can be run onsite in secondary or tertiary care settings. It uses the same biopsy sample used to diagnose melanoma. The assay should be read by a trained histopathologist along with the haematoxylin and eosin (H&E) slide of the same tissue used to diagnose melanoma. AMBLor may be used after initial staging of non-ulcerated stage 1 to 2B melanomas to identify people with low-risk disease. It may help healthcare professionals assess if a sentinel lymph node biopsy is needed. The company advises that the test should take no more than 20 minutes to complete when done in NHS settings.

Newcastle upon Tyne NHS Hospitals Trust also has UK Accreditation Service approval for a separate send-away service for NHS settings that do not have onsite testing. This service uses the AMBRA1 and loricrin antibodies used in AMBLor. The send-away service takes around 5 days from receiving samples to delivering the report.

Costs

Technology costs

AMBLor costs £175 per test (excluding VAT). Only 1 test is needed per biopsy analysis. The company estimates additional processing costs of £20 per test for tests done in NHS settings. This includes costs associated with:

  • preparing the sample and slides, including quality control staining, by a band 6 biomedical scientist

  • scoring of the slides by a histopathologist

  • writing the report.

Online training for pathologists is available through the company at no cost. The company estimates that the send-away service will cost £300 to £400 (excluding VAT).

Costs of standard care

AMBLor is an addition to standard care.

AMBLor is intended to enhance follow-up care and may reduce the frequency of follow-up appointments. The average cost of consultant led dermatology non-admitted face-to-face follow up (WF01A) is £123 per appointment (using the 2019/20 national schedule of NHS costs).

The company claims that AMBLor may also reduce the use of sentinel lymph node biopsies in people with AMBLor low-risk non-ulcerated stage 1B to 2B melanomas. There is currently no evidence of this.

NICE's guideline on melanoma: assessment and management (2015) estimated that the additional cost of sentinel lymph node biopsy alongside wide excision was £2,088 per person (using 2012/13 NHS reference costs). The company estimates this would be £2,309 when inflated to 2019/20 costs. There may also be additional costs for follow-up appointments and potential complications from the procedure.

Resource consequences

The antibodies that are used in the AMBLor test have been accredited by the UK Accreditation Service and are used in 1 NHS trust. The company states that the technology fits into the current care pathway with little change needed to existing processes. The AJCC staging system is limited by the heterogeneity of tumours. AMBLor may improve prognostic risk stratification for early-stage non-ulcerated primary cutaneous melanomas. It may better identify people with low risk who may benefit from more conservative treatment. The company claims this could reduce the frequency of follow-up appointments, the need for sentinel lymph node biopsies, and may lessen the worries of patients.

AMBLor may be more cost effective and affordable than the current frequency of follow ups in standard care for stage 1 melanoma (Coughlan et al. 2019). A budget impact assessment by the company suggests that AMBLor could be cost saving when compared with standard care. Cost savings may range from £2 (stage 1A) to £245 (stage 2A) per person, with average savings of £175 per person.