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Return of Clinically Actionable Pharmacogenetic Results From Molecular Tumor Board DNA Sequencing Data: Workflow and
Hyunwoo Koo1,2, Tayler B Smith1,3, John T Callaghan1,4
1Division of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Abstract:
Pharmacogenetic testing can prevent severe toxicities from several oncology drug therapies; it also has the potential to improve the outcomes from supportive care drugs. Paired tumor and germline sequencing is increasingly common in oncology practice; these include sequencing of pharmacogenes, but the germline pharmacogenetic variants are rarely included in the clinical reports, despite many being clinically actionable. We established an informatics workflow to evaluate the clinical sequencing results for pharmacogenetic variants. We used the Aldy computational tool, which we have previously shown to determine the variant alleles in 14 pharmacogenes in clinical sequencing data with >99% accuracy, to identify pharmacogenetic variants in the clinical whole exome sequencing from our molecular tumor board. Patients with genetic variants that are clinically actionable for their individual therapy programs, including both treatment and supportive care, are referred to a clinical pharmacogenetics testing laboratory for confirmation. Through an evaluation of our weekly informatics workflow, we determined it took approximately 3.25 hours to complete the analysis of the sequencing data from approximately 20 patients. Using a United States pharmacist's median salary, we estimated the incremental added cost of the process to be only ~$15 per patient. This adds only a minor increase to the patient's cost of testing and has the potential to improve the safety and efficacy of their treatment.
Insights
Integrating pharmacogenetic (PGx) testing into oncology care can prevent drug toxicities and improve treatment outcomes. This study developed an efficient informatics workflow to identify actionable PGx variants from clinical sequencing data, enhancing patient safety and treatment efficacy.
Area of Science:
- Oncology
- Pharmacogenomics
- Bioinformatics
Background:
- Pharmacogenetic (PGx) testing is crucial for preventing severe toxicities from oncology drugs and optimizing supportive care.
- Clinical tumor and germline sequencing often includes pharmacogenes, but actionable PGx variants are frequently omitted from reports.
- Integrating PGx variant analysis into routine clinical practice is essential for personalized cancer therapy.
Purpose of the Study:
- To establish an informatics workflow for identifying clinically actionable pharmacogenetic variants from routine clinical sequencing data.
- To evaluate the efficiency and cost-effectiveness of this workflow in an oncology setting.
- To facilitate the integration of PGx information into patient treatment plans.
Main Methods:
- Utilized the Aldy computational tool for accurate identification of variant alleles in 14 pharmacogenes from clinical whole exome sequencing data.
- Developed and evaluated a weekly informatics workflow for processing sequencing data from molecular tumor boards.
- Referred patients with actionable PGx variants for confirmation at a clinical pharmacogenetics testing laboratory.
Main Results:
- The informatics workflow accurately identified pharmacogenetic variants with >99% accuracy.
- Analysis of sequencing data for approximately 20 patients took about 3.25 hours.
- The estimated incremental cost per patient was approximately $15, based on a US pharmacist's median salary.
Conclusions:
- The developed informatics workflow is efficient and cost-effective for identifying actionable pharmacogenetic variants in oncology patients.
- Integrating this workflow into clinical practice can enhance the safety and efficacy of cancer treatments.
- Routine reporting of germline pharmacogenetic variants from clinical sequencing holds significant potential for personalized medicine.
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