[Targeted next-generation sequencing of gene panels for the pharmacogenetics of acute leukaemia and supportive care treatments.]
Low E, Zeghari-Squalli N, Carbonneil C
Record ID 32018014797
French
Original Title:
Séquençage haut débit ciblé des panels de gènes en pharmacogénétique des traitements d’oncologie et des soins de support des leucémies aiguës – Recherche des variants génétiques constitutionnels
Authors' objectives:
The objective of this assessment was to determine the clinical value of using targeted NGS gene panels to identify genes involved in the pharmacogenetics of acute leukemia (myeloblastic and lymphoblastic) treatments and supportive care treatments.
The aims were:
(1) to identify genes and genetic variants of interest for dose adjustments in acute leukaemia and supportive care treatments;
(2) if data were available, to define the diagnostic yield of specified gene panels;
(3) to describe the role of targeted next-generation sequencing (NGS) gene panels in the overall treatment strategy for patients with acute leukaemia.
Authors' results and conclusions:
This assessment analysed data demonstrating that the use of NGS gene panels for pharmacogenetics in acute leukaemia and supportive care enables the following:
- the early detection of deleterious variants of the TPMT and NUDT15 genes, which can prevent haematological toxicity related to thiopurines (mercaptopurine in adults and children, and thioguanine in children). This reduces the therapeutic dose required.
- the prevention of toxicity or optimisation of the efficacy of codeine and tramadol through early detection of CYP2D6 gene variants. This allows the therapeutic dose of codeine or tramadol to be adjusted as required in adult and paediatric populations.
- Diagnosis of non-response to ondansetron and tropisetron in adults through early detection of CYP2D6 gene variants, enabling an increase in the therapeutic dose.
- diagnosing non-response to omeprazole, pantoprazole and lansoprazole in adults and children by identifying CYP2C19 gene variants early on, which enables an increase in the therapeutic dose.
- the prevention of ibuprofen toxicity in adults by identifying deleterious variants of the CYP2C9 gene that affect ibuprofen metabolism. This enables the therapeutic dose to be reduced.
The literature search identified no systematic reviews, meta-analyses or clinical guidelines confirming the diagnostic yield or the role of targeted gene panel analysis in relation to monogenic techniques. However, the consulted experts emphazised that SHD gene panel analysis has significant technical advantages over targeted allele discrimination techniques such as PCR or Sanger sequencing. Notably, SHD simultaneously covers genes of interest and detects rarer variants than those traditionally identified by conventional techniques, which mainly focus on specific hotspots.
In the absence of formal evidence attesting to the superiority of SHD over targeted allele discrimination techniques in terms of diagnostic yield, the HAS allows each laboratory to select the technique best suited to their organization.
Authors' recommendations:
The French National Authority for Health recommends funding by the National Health Insurance for the medical service of next generation sequencing of the genes panels specified in the conclusions and results.
Targeted gene panel testing (including the TPMT and NUDT15 genes) should be performed upon a confirmed diagnosis of acute leukaemia, prior to treatment in the post-induction phase for patients requiring thiopurine treatment (e.g. mercaptopurine or thioguanine) as part of consolidation or maintenance chemotherapy.
For supportive care treatments, gene panel testing may be performed at the clinician's discretion as part of a confirmed acute leukaemia diagnosis, either before or after chemotherapy is initiated.
This is specifically recommended for patients with a history of unusual toxicity (grades I to III) following prescribed supportive treatment.
These lists of genes may change in the future based on assessments by the HAS.
Authors' methods:
This assessment was based on the following three methods:
(1) A critical analysis of systematic reviews, meta-analyses and clinical practice guidelines, which were identified through a systematic search and selected based on PICO criteria.
(2) The identification of the level of evidence of genetic variants of interest, according to the Clinical Pharmacogenetics Implementation Consortium (CPIC®) and ClinPGx databases.
(3) Consultation with professional experts, stakeholders (including relevant professional bodies and patient/consumer organizations) and public health institutions.
Authors' identified further research:
The French National Authority for Health emphasizes that the composition of these next-generation sequencing gene panels may change over time. New assessments will be conducted as scientific knowledge evolves.
Details
Project Status:
Completed
Year Published:
2025
Requestor:
Ministry of Health, Families, Independence, and People with Disabilities.
English language abstract:
There is no English language summary available
Publication Type:
Full HTA
Country:
France
MeSH Terms
- Leukemia
- Leukemia, Myeloid, Acute
- Genetic Testing
- High-Throughput Nucleotide Sequencing
- Pharmacogenomic Testing
Keywords
- Pharmacogenetics
- Next-generation sequencing
- Gene panel
- acute leukemia
- supportive care
Contact
Organisation Name:
Haute Autorité de Santé
Contact Address:
2 avenue du Stade de France, 93218 Saint-Denis La Plaine Cedex, France. Tel: +33 01 55 93 71 88; Fax: +33 01 55 93 74 35;
Contact Name:
has.seap.secretariat@has-sante.fr
Contact Email:
has.seap.secretariat@has-sante.fr
Copyright:
<p>Haute Autorite de Sante/French National Authority for Health (HAS)</p>
This is a bibliographic record of a published health technology assessment from a member of INAHTA or other HTA producer. No evaluation of the quality of this assessment has been made for the HTA database.