1. Nalley, Catlin

Article Content

New analyses from the ADAGIO study presented at the ASCO 2021 Annual Meeting challenge the tolerance for nonadherence to imatinib among patients with chronic myeloid leukemia (Abstract 7038).

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"Imatinib changed chronic myeloid leukemia from a lethal disease-with very little life expectancy and brutal treatment-to a chronic condition," noted study author Ivo Abraham, PhD, Professor, Center for Health Outcomes and PharmacoEconomic Research, The University of Arizona. "In fact, a number of the patients in the original IRIS trial that led to the approval of imatinib are still alive 20 years later."


"ADAGIO was the first study that explored adherence in these patients," he continued. "Approximately one-third of patients admitted to being non-persistent. So, the question became, is there a margin for nonadherence?"


While the importance of adherence to imatinib treatment has been established among CML patients, some studies have suggested a 7.3 percent to 9.9 percent nonadherence tolerance margin before loss of treatment effects, according to study author Mavis Obeng-Kusi, BPharm, MPharm, Center for Health Outcomes and PharmacoEconomic Research, The University of Arizona.


"In this current analysis, we sought to determine the margin of tolerance required to ensure treatment response among patients prescribed imatinib and the margin, if any, before treatment response is at risk," she explained.


"Our goal was to be able to inform clinicians as well as patients and help them understand the importance of adhering to this medication," Obeng-Kusi elaborated. "It is normal to occasionally miss a dose, but we need to emphasize how critical adherence is to ensure optimal treatment responses."


Research Findings

Obeng-Kusi and colleagues performed a post hoc analysis of the ADAGIO study, which included 169 evaluable patients (Blood 2009;113(22):5401-11). The researchers used the pill count ratio as the time variable and modeled the cumulative likelihood of treatment response as a function of increasing pill count adherence.


"We applied Kaplan-Meier methods to model the likelihood of complete cytogenetic (CCyR), complete hematological (CHR), major molecular (MMR), and optimal (OR) response as a function of 90-day pill count adherence," explained Obeng-Kusi. "Kaplan-Meier methods estimated the tolerance for nonadherence to imatinib by calculating the one minus Kaplan-Meier estimate for treatment response."


Data showed that 100 percent adherence of the prescribed dose is associated with probabilities of 0.84 for CHR, 0.83 for CCyR, 0.82 for OR, and 0.77 for MMR. Comparatively, the probabilities at 90 percent adherence were 0.37 (CHR and CCyR), 0.35 (OR), and 0.39 (MMR).


The likelihood of the various treatment responses increased by 1.95- to 2.35-fold when the intake of imatinib went from 90 percent to 100 percent of the prescribed dose, according to the investigators.


"Imatinib is an unforgiving drug with virtually no margin for non-adherence," noted Obeng-Kusi. "One hundred percent adherence is associated with approximately a two-fold increase in achieving CHR, CCyR, MMR, and optimal response. So, it is not just about prescribing the medication. Clinicians must also be committed to assessing and promoting patient adherence."


What can be done to encourage medication adherence among patients? It begins with engagement and education, suggested Obeng-Kusi. "Medical care is moving away from the more traditional setting where the practitioner was in charge to a place where we are actually involving the patients more in their therapy," she told Oncology Times. "And so, as this shift continues, it's important that the clinicians are engaging their patients. The patient needs to be educated and given the right resources for success.


"It's not just about prescribing medicine. Clinicians must be invested in what is going on with their patients at a more granular level," she emphasized. "We must involve them in their therapy so they can understand their conditions better. I believe patients will become more committed because they are taking control of their treatment and are part of the team that is making these decisions."


Catlin Nalley is a contributing writer.