Feasibility and value of incorporating pharmacogenomic testing for genetic variants in UGT1A1 and DPYD genes in patients receiving irinotecan and/or 5-fluorouracil chemotherapy.

Abstract

814 Background: The importance of pharmacogenomics in optimizing drug doses and avoiding adverse events is increasingly being recognized. The FDA has listed pharmacogenomic biomarkers as part of drug labeling in many medications including chemotherapies such as 5-fluorouracil and irinotecan. Pharmacogenomics may enable selection of the most tolerable treatment without compromising treatment success. Variation in the dihydropyrimidine dehydrogenase ( DPYD) and UGT1A1 gene mutations can increase the risk of 5-FU and irinotecan based chemotherapy respectively. Also, the feasibility of testing in real-time and incorporating results into management has not been demonstrated. The focus of our study was to demonstrate this in the real world scenario as a quality improvement project. Methods: In July-August 2017, 89 patients who were on irinotecan and/or 5-FU chemotherapy were tested for DPYD and UGT1A1 genetic variations at Mayo Clinic Florida. Testing was done through blood sample which was collected at routine clinic visit prior to starting therapy or in patients already receiving chemotherapy. Pharmacy electronic consultation was obtained for recommendations regarding current and/or future chemotherapy regimens, based on pharmacogenomics results. A medication therapy management (MTM) consultation from the pharmacist was incorporated and included into the patient’s chart. Results: Total number of patients who has some variation in the UGT1A1 and/or DPYD gene was 60 (67%). Specifically, there were 12 patients who were homozygous for the UGT1A1 gene and 3 homozygous for DPYD gene. Both genes were affected in 3 patients. One patient was triple heterozygous for DPYD and homozygous for UGT1A1. Pharmacogenomic results were obtained for these patients within 5 business days. Conclusions: A higher prevalence of UGT1A1 and DPYD variants were reported in our patient cohort tested than what is reported in the literature. Additionally, we were able to obtain results for these patients in a timely fashion. This was then further incorporated into medication therapy management consultation from the pharmacist, which added further value.