Simpler 6-MP Administration in ALL May Improve Adherence

Administration restrictions on oral mercaptopurine (6-MP) are unnecessary and may impair adherence among children with acute lymphoblastic leukemia (ALL), according to a study published in the Journal of Clinical Oncology.¹

Maintenance therapy with 6-MP is standard of care for children with ALL, though previous studies showed low levels of patient adherence. Patients are typically directed to take 6-MP at night without food or dairy products. The purpose of this study was to determine if administration habits of 6-MP affect adherence and risk of relapse.

In this prospective, observational study, 441 children with ALL receiving maintenance therapy with 6-MP were evaluated for adherence, administration habits, and relapse. Adherence was monitored by the Medication Event Monitoring System, and administration habits were parent-reported by questionnaire at 4 study time points.

At study entry, the median age was 6 and 67% were male. The cohort consisted of 33.8% non-Hispanic whites, 35.8% Hispanics, 145.4% Asians, and 15% African Americans. All patients harbored the wild-type variant of TPMT.

The study found that 43.8% of children were non-adherent, defined as an adherence rate of less than 95%. Taking 6-MP with dairy (odds ratio [OR], 1.9; 95% CI, 1.3-2.9; P = .003) and at varying times (OR, 3.4; 95% CI, 1.8-6.3; P = .0001) was significantly associated with non-adherence.

6-MP administration habits — taken with food or dairy, taken at night or at varying times — were not associated with risk of relapse, after adjusting for adherence and other prognostic factors.

Red cell thioguanine nucleotide levels were not affected by administration habits among adherent children.

The authors recommend that simpler administration may improve adherence. “Recommendations to take 6-MP in the evening in a fasting state — aimed at enhancing 6-MP absorption — may present barriers to adherence and are probably unnecessary,” the authors wrote.

Reference

1. Landier W, Hageman L, Chen Y, et al. Mercaptopurine ingestion habits, red cell thioguanine nucleotide levels, and relapse risk in children with acute lymphoblastic leukemia: a report from the Children’s Oncology Group Study AALL03N1. J Clin Oncol. 2017 March 24. doi: 10.1200/JCO.2016.71.7579 [Epub ahead of print]