A cost effectiveness analysis of thiopurine methyltransferase testing for guiding 6‐mercaptopurine dosing in children with acute lymphoblastic leukemia

Abstract

The present analysis suggests that screening for TPMT mutations using either genotype or enzymatic laboratory tests prior to the administration of 6-MP in pediatric ALL patients is not cost-effective.

Adverse Drug Reactions

“…Genotype-directed dosing schedules compared favorably with other dosing schedules, with pretreatment genotyping costing $579 per life-year saved for a 30-year-old and $1364 per life-year saved for a 60-year-old [75]. Incremental costs per child (95% confidence interval) were $277 and $298 for the genotyping and phenotyping strategies, respectively, compared to weight-based dosing [81]. However, a recent cost-effectiveness analysis in children with acute lymphoblastic leukemia (ALL) reported that screening for TPMT mutations using either genotype or enzymatic laboratory tests prior to administration of 6-MP in pediatric ALL patients did not demonstrate any survival benefit and was therefore not cost-effective.…”

Analyzing the clinical actionability of germline pharmacogenomic findings in oncology

“…Several gene/drug examples have been described for decades, 1 with various degrees of implementation across oncology institutions and practices. [42][43][44] We used a previously published method 19 to critically assess the vast number of germline pharmacogenomic studies about oncology drugs. It is noteworthy that the majority of drugs have had positive pharmacogenomic associations described about them (67 of the 125 drugs), with published associations for 12 drugs withstanding rigorous evidence standards required for clinical actionability.…”

Pharmacokinetic and pharmacogenetic determinants and considerations in chemotherapy selection and dosing in infants

“…This label change applied to pediatric cases since the pharmacogenetics of thiopurine in children has been directly studied [76][77][78]. Routine testing of TPMT activity prior to administration of azathioprine has been suggested to decrease deaths from neutropenic sepsis and improve quality of life [79]; however, routine testing at diagnosis in pediatric ALL has been controversial and considered by some to be non-cost-effective [80], as testing can be done later in patients with unexpectedly severe myelosuppression and adjustments made at that stage.…”