clonoSEQ (Adaptive Biotechnologies) is a diagnostic medical device. It uses multiplex polymerase chain reaction (PCR) and next generation sequencing (NGS) to differentiate between malignant cells and normal healthy cells. The technology is used to quantify minimal residual disease (MRD) in people with multiple myeloma, acute lymphoblastic leukaemia (ALL) and chronic lymphocytic leukaemia (CLL). MRD is the term given to the small number of leukaemic cells that remain in the blood or bone marrow during treatment, or after treatment when the person is in remission. These cells can eventually cause disease recurrence. MRD assessment is commonly used clinically to evaluate how much the cancer has responded to treatment, categorise the risk of relapse and help decision making. MRD assessment is usually done after initial induction therapy and at additional time points based on the regimen used. The company has stated that people usually have testing for MRD at baseline, and then from 1 to 4 times per year depending on disease severity. clonoSEQ can identify and track individual cancer cells over time, so each cell's DNA sequence can be assessed in subsequent MRD samples.
clonoSEQ uses NGS, which is an alternative to traditional MRD measurement such as flow cytometry. The company claims that NGS has shown enhanced sensitivity and specificity of sequenced-based assays compared with flow cytometry for MRD determination. clonoSEQ uses proprietary bioinformatics and analytics to generate clinically relevant and quantitative results from complex datasets. Also, laboratories using standard techniques may use different preparation procedures, reagents and reporting methods, which is a significant limitation in terms of standardisation. NGS is intended to address these issues.
Clinical feedback suggests that MRD testing is standard practice across treatment centres in England for people with ALL. It is only done for certain people with multiple myeloma and CLL. MRD status is a major predictive factor of relapse for people in remission, so MRD assessment is usually done after starting induction therapy when complete remission is first seen. Current methods of MRD assessment include flow cytometry and PCR. Flow cytometry is a technique when antibodies are used to bind to different cell markers on cells. These antibodies are tagged with a fluorescent molecule to be detected and allow specific proteins to be identified on the cell. PCR also uses fluorescent markers to bind to newly synthesised DNA strands from a specific gene of interest.
The following publications have been identified as relevant to this care pathway:
clonoSEQ is intended for people with multiple myeloma, ALL and CLL during treatment or after remission. For multiple myeloma, MRD testing is not usually done until a person is in complete remission. The technology is likely to be used in specialist centres by haematologists or oncologists.
The cost of the clonoSEQ assay has not yet been decided in the UK. The company has advised that the list price of the assay in the UK will be in the range of £1,100 to £1,400 per unit.
The technology is not currently used in the NHS, but the company estimates that about 50,000 to 75,000 people a year would be eligible for MRD assessment using clonoSEQ.
It is unclear whether any changes in facilities or infrastructure would be needed with adoption of the technology.