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6-mercaptopurine intake often over-reported during pediatric ALL maintenance therapy
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ORLANDO, Fla. — Over-reporting of 6-mercaptopurine intake appeared common during maintenance therapy for patients with childhood acute lymphoblastic leukemia, according to a Childhood Oncology Group study presented at the ASH Annual Meeting and Exposition.
Thus, subjective reporting of 6-mercaptopurine (6MP) during maintenance therapy for childhood ALL may be unreliable and should be interpreted with caution, according to the researchers.
Wendy Landier
“Durable remission of childhood ALL requires approximately 2 years of maintenance chemotherapy that relies on a backbone of daily oral 6MP,” Wendy Landier, PhD, CRNP, associate professor of pediatrics at University of Alabama at Birmingham, said during a press conference. “We have previously shown that electronically measured 6MP adherence rates under 95% are associated with a 3.7-fold risk for relapse. Accurate intake of 6MP usage is therefore crucial to ensure timely intervention for non-adherent patients.”
Although self-reporting is convenient and inexpensive, literature in the non-oncology setting has suggested that self-reporting is subject to over-reporting, the extent of which is directly related to the number of missed doses.
Thus, Landier and colleagues sought to observe the accuracy of patient- or parent-reported intake of 6MP during ALL maintenance compared with electronic monitoring.
The study included 416 children with ALL (median age, 6 years; 67% boys) in first remission. Patients were taking 75 mg/m2 oral 6MP daily during maintenance.
The researchers monitored 6MP intake electronically using the Medication Event Management System (MEMS), which recorded the dates and times of each 6MP bottle opening over 4 study months per patient.
Objective and subjective records of 6MP intake were compared for each patient by study month, with patients categorized as “perfect reporters” (self-report equals the MEMS report), “over-reporters” (self-report is greater than the MEMS report by ≥ 5 days per month for > 50% of study months) and “others.”
According to the researchers, 38.4% of study participants had high-risk disease and 40.4% were nonadherent to oral 6MP.
The mean days of 6MP ingestion per month ranged from 25.8 ± 5.3 to 26.1 ± 4.5 by subjective reporting (P < .0433) vs. 22.8 ± 6.4 to 25.4 ±4 .5 by objective observation (P < .0001). The correlation between self-report and MEMS by study month ranged from 0.36 to 0.58.
The researchers identified 50 patients (12%) as perfect reporters. Ninety-eight patients (23.6%) were over-reporters, with the remaining patients (64.4%) categorized as others.
Independent predictors of over-reporting included older age (OR = 1.07; 95% CI, 1-1.1), Hispanic race (OR = 2.4; 95% CI, 1.2-5), Asian race (OR = 3.1; 95% CI, 1.2-8.3), black race (OR = 5.3; 95% CI, 2.2-12.5), having a non-college educated father (OR = 2.1; 95% CI, 1.1-4.1) and 6MP nonadherence (OR = 8.6; 95% CI, 4.7-15.9).
According to the researchers, nonadherent patients comprised 78.6% (n = 77) of over-reporters and 2% (n = 1) of perfect reporters.
In an interview with HemOnc Today, Landier highlighted strategies for increased patient education, which may lead to improved adherence.
“In an ongoing clinical trial, we have developed a multimedia educational program that each patient watches with their family,” Landier said. “The program has interviews with families who have gone through the process, as well as information about why the medication is important, and why it is important to take it on an ongoing basis. It also has advice from families about how they remember to take their medicine. It is good practical advice from people who have gone through the process.” – by Cameron Kelsall
Reference:
Landier W, et al. Abstract 82. Presented at: ASH Annual Meeting and Exposition; Dec. 5-8, 2015; Orlando, Fla.
For more information:
Wendy Landier, PhD, CRNP, can be reached at wlandier@peds.uab.edu.
Disclosure: Two study researchers report royalties from a patent for TPMT genotyping. Landier and the other researchers report no relevant financial disclosures.
Perspective
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Mark Crowther, MD, MSc, FRCPC
The study by Landier and colleagues is extremely important. You are going to see numerous presentations at this meeting about new, novel therapies. Some are expensive, some are complex and some are revolutionary. But if the patients do not take them, they cannot possibly work. The issue of how to maximally use the therapies we currently have available is a huge problem for medicine. It is great to have advances, but we need to spend a bit of time to make sure that we use the therapies we have now appropriately. If a medication fails, we need to know if it is because it didn’t work, or if it is because the patient was not taking it.
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Ryan D. Cassaday, MD
It has been previously shown that suboptimal adherence — which was defined as less than 95% adherence to doses administered — was associated with an inferior outcome. In this study, Landier and colleagues evaluated not only a patient’s self-reported adherence to therapy, but they also used an electronic system that was on the pill bottle itself that registered how often the pill bottle was opened as a surrogate for times the pills were actually ingested. What they found — perhaps not surprisingly — was that patients generally are much more optimistic about how closely adherent they are to their treatment compared with the more objective, electronic system on the pill bottle. Pretty much across the board, patients were over-reporting how much of the 6-mercaptopurine they were taking. There were very few patients who were close to what they said they self-reported vs. what the pill bottle said.Overall, these data show that not taking your 6-mercaptopurine appropriately is associated with a greater chance for relapse. But most importantly, trying to pin down exactly how much the patient is taking is probably not best done by relying on self-reporting. More objective measures like this type of tool may be a better way to monitor patients, particularly moving ahead in clinical trial settings and potentially even in routine clinical practice, to intervene on a patient who is not taking their therapy the way they should be.
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