The importance of routine G6PD screening in oncology patients: A prospective comparative study in African American males (AAM) highlighting the additional benefits of pharmacogenomics (PGx) panels over standard enzyme assay.
Authors: Srishti Sareen, Rahul Reddy Tirumalareddy, Mark Mitchell, Jaya Adabala, Mirza Mashaal Khan, Katie Stoops, Jacob Marler, Lindsey Lands, Alva Bowen Weir
Journal: Journal of Clinical Oncology (2025)

e13838 Background: G6PD deficiency can cause acute hemolytic anemia due to oxidative stress in red blood cells triggered by medications. It has traditionally been diagnosed using enzyme activity assays which are influenced by various factors, potentially limiting their accuracy. Genetic testing offers a more reliable alternative. In this study, G6PD genotype testing was performed as part of a 16-gene Pharmacogenomics (PGx ) panel on all AAM patients attending VA Hematology-Oncology clinic to identify genetic enzyme deficiencies that could increase chemotherapeutic toxicities. This study is the first to compare enzymatic assays and PGx panels for G6PD testing in adult AAM, particularly in hematology-oncology patients who are more likely to receive high risk medications. Methods: We investigated the sensitivity, specificity, concordance, clinical utility and cost-effectiveness of a PGx panel versus enzyme assays for diagnosing G6PD deficiency in adult AAM at a US Veteran Hematology/Oncology Clinic. From May 15, 2024, to January 3, 2025, 156 patients provided verbal consent and were tested using a VA-funded 16-gene PGx panel (analyzing CYP2C, CYP2C9, CYP2C19, CYP2D6, DPYD, TPMT, CYP4F2, VKORC1, SLCO1B1, CYP3A5, UGT1A1, ABCG2, CYP2B6, G6PD, HLA-B*57:01, and NUDT15 ) alongside a standard G6PD enzyme assay. Results: The prevalence of G6PD deficiency was higher in our cohort (15%) compared to the literature (10%). There was a concordance rate of 97.8% between the two assays, and similar sensitivity and specificity between the two methods. One patient’s G6PD status was reclassified based on the PGx assay in this small population. Most patients had genitourinary or gastrointestinal malignancies. In addition to the G6PD information, PGx findings impacted actionable phenotypes (current medications requiring dose adjustments) in 61% of patients, while 538 informational phenotypes (future medications potentially requiring dose adjustments) were identified. PGx analysis revealed genetic variations impacting the following chemotherapeutics if ever prescribed: capecitabine (in 4% patients) and irinotecan (15% patients dose adjust, 55% monitor closely), supported by moderate to strong evidence. Conclusions: In this prospective comparative study, PGx panel provided valuable insights regarding G6PD status, and additional genetic variations affecting chemotherapy metabolism in an AAM oncology population. The enzymatic assay is less expensive ($3 vs. $225), but PGx testing delivers broader therapeutic insights that could impact hematology-oncology care. Further cohort expansion will assess the impact of PGx-detected polymorphisms on chemotherapy dosing in our patient population, including the impact of UGT1A1 intermediate metabolizers in patients receiving irinotecan.