Studying the Impact of Imatinib Mesylate (IM) Adherence in Chronic Myeloid Leukemia (CML) patients’ Responses in the State of Qatar
Authors: Al-Dewik Nader I , Morsi Hisham , Ghasoub Rola , Yassin Mohamed A. 
Published: October 2019

Abstract
Background:
The introduction of Imatinib Mesylate (IM) has revolutionized the outcome of Chronic Myeloid Leukemia (CML) patients. However, the success of the rationally designed therapy is tempered by the understanding that a substantial proportion of CML patients fail treatment.
In Qatar, 54% of CML patients do fail IM according to European leukemia net (ELN) recommendations 2013. Point mutation & unique tri-nucleotide insertions explained only 14% of treatment failure. Additional chromosomal abnormalities were the most common cause of IM failure in our patients’ cohort & were documented in 50% of cases. 14% of patients stopped IM due to intolerance & the mechanisms of resistance remained unknown in 28% of patients. Other cause such as patients’ adherence to IM is being prospectively investigated. Therefore, Non adherence to IM must be ruled out as a possible cause of lack of optimal response before considering such patients to be IM-resistant & switching them to next-line treatment.
Aim:
To correlate between CML patients’ adherence to IM treatment & their responses and identify the factors affecting non-adherence.
Methods:
36 CML patients (5 citizens & 31 residents) are consented into the study. adherence to Imatinib was assessed using four different techniques: calculation of the Medication Possession Ratio (MPR), electronic Medical Records (eMR), survey questionnaire & Medication Event Monitoring System (MEMS).
MPR is defined as the sum of the days' supply of medication divided by the number of days between the first fill & the last refill. Patients medications history was obtained from questionnaire, pharmacy electronic Medical record (eMR) & studying drug – drug interactions was done using MICROMEDEX® 1.0 (Healthcare Series).
The Questionnaire used to identify potential factors revolving around the patient's lifestyle, affordability & knowledge related to IM, in addition to standardized evaluation based on the 9-item Morisky Medication Adherence Scale (MMAS) ranging from 1 to 13. Scores ≤10 indicates non adherence whereas ≥ 11 indicates adherence.
Patient adherence was tracked electronically using the Medication Electronic Monitoring System (MEMS) that provided real time measures of adherence for a period up to 4 months.
95 Peripheral blood (PB) samples were collected & the level of BCR-ABL1 transcripts was measured via RT-QPCR.
The ELN 2013 recommendations for the management of CML was adopted & employed in this study to assess the response/resistance of patients to treatment. Responses were defined at the haematological, cytogenetic & molecular levels. Patients responses were classified into optimal, suboptimal or failure.
Results:
Out of 36 patients, 23 patients were adherent (MMAS, MPR &MEMS were ≥ 80%) & 13 patients were classified as non-adherent (MMAS, MPR &MEMS were <80 % )
All adherent patients were optimally responded to the treatment (achieved CCyR & MMR) while the 13 non-adherent patients failed the treatment (2 patients were intolerant, 9 patients did not achieved CCyR & molecular response & 2 patients developed additional chromosomal abnormalities.
Questionnaire feedback results showed that 69% patients could not afford to pay the remaining 10% of its cost, the other factors such as lack of knowledge (comprehensive & insight of illness) & illiteracy were observed in 35% & 30% of patients respectively.
Discussion & conclusion:
Due to high rate of Imatinib failure in Qatar, patient’s adherence to treatment was studied. Non adherence to the treatment was one of the most common causes of Imatinib failure in our patients’ cohort & was documented in 36% of cases.
Economic factor (Unaffordable drug price) was one of the main causes of non-adherence & efforts should be made locally to improve access to medications for cancer diseases.
Other risk factors associated with poor adherence can be improved by close monitoring & dose adjustment. Monitoring risk factors for poor adherence in combination with patient education that includes direct communication between the health care teams doctors, nurses pharmacists & patients are essential components for maximizing the benefits of TKI therapy & could rectify this problem.
Our preliminary results showed that patients’ response to treatment may be directly linked to patient adherence to the treatment. However, further in-depth & specific analysis may be necessary in a larger cohort.

Disclosures
Al-Dewik: Hamad Medical Corporation (HMC): Employment, HMC Medical Director's Grant Competition (GC) 1013A Patents & Royalties, Research Funding. Morsi:HMC: Employment, Research Funding. Ghasoub:HMC: Employment, Research Funding.