Associations Between Treatment Restrictions, Patient-Reported Treatment Burden and Adherence to Tyrosine-Kinase Inhibitor Therapy Among Chronic Myeloid Leukemia Patients in the United States and Europe

The availability of the tyrosine-kinase inhibitor (TKI), imatinib, and later introduction of second generation TKIs, dasatinib and nilotinib, have not only improved the clinical outcomes of patients with chronic myeloid leukemia (CML), but have also provided multiple therapeutic options for CML patients. Despite the widespread use of these oral therapies, little is known about the impact of different treatment regimens on overall treatment burden and adherence among CML patients.

The objective of this cross-sectional survey conducted in the United States (US) and Europe (EUR) was to assess the overall CML disease management and treatment experience from the patient's perspective. This analysis evaluates the impact of dosing and dietary restrictions on patient-reported adherence and difficulty following oral TKI treatment regimens.

This study included patients identified from the National Health and Wellness Survey and Lightspeed Research Chronic Illness Panel aged ≥18 years from the US and EUR (United Kingdom, Spain, France, Italy, and Germany) who had a diagnosis of CML, were in chronic phase, and were currently on TKI treatment or on a drug holiday. Patients completed a web based self-administered questionnaire. Relevant measures of treatment restrictions, including dietary restrictions (while fasting, with food, without certain foods, with water, at specific time intervals, or without certain non-CML meds) and dosing regimens (once a day, twice a day, two or more pills at one time, or at specific times of day) were compared across TKIs. Outcomes included CML treatment adherence (TKI dose was missed/skipped or taken less than prescribed over the past 4 weeks) and treatment difficulty (patient-reported difficulty in following treatment regimens - Yes/No). A composite score of overall dietary restrictions was constructed for each patient to assess associations with patient-reported treatment difficulty and adherence using a structural equation model (SEM).

A total of 303 respondents participated in the study (50% from US), of which 68.6% reported current treatment as imatinib, 12.5% dasatinib and 16.2%nilotinib (2.7% reported other). Mean age was 51.5 years (standard deviation [SD] = 13.6), 46.2% were male, and mean time since diagnosis was 4.8 years (SD = 4.5), with 12.3% of patients within 12 months of diagnosis. The majority of patients reported being adherent to their CML treatment, with 25.4% stating missed doses within the past 4 weeks. Approximately 30% reported difficulty in following treatment regimens; treatment difficulty was substantially higher among nilotinib (63.3%) than among dasatinib (3.7%) or imatinib (22.9%) treated patients (p<0.0001). Overall dietary restriction scores (ranging from -1.33 to 1.60, with positive values indicating greater restrictiveness) were low among dasatinib (mean score= −0.31) and imatinib users (-0.06), whereas overall scores were significantly higher among nilotinib users (mean= 0.61; p<0.0001). Although dietary restrictions were not significantly associated with self-reported adherence (p=0.24), results of the SEM model indicated that higher overall dietary restriction scores were associated with significantly greater difficulty in taking medication as required (beta=0.28, p<0.001).

Dietary restrictions were strongly associated with patients reporting difficulty with current treatment regimens. Patients receiving dasatinib and imatinib reported fewer dietary and dosing restrictions than did patients receiving nilotinib. Choosing a regimen that requires fewer overall dosing restrictions may be an important consideration for treatment choice in CML patients.

Gupta:Bristol-Myers Squibb: Research Funding. Goren:Bristol-Myers Squibb: Research Funding. Victor:Bristol-Myers Squibb: Research Funding. Chapnick:Bristol-Myers Squibb: Research Funding. Hawthorne:Bristol-Myers Squibb: Research Funding. Hirji:BMS: Employment. Olavarría:Bristol-Myers Squibb: Consultancy. Moadel:Bristol-Myers Squibb: Consultancy. Lemoine:Bristol-Myers Squibb: Consultancy. Davis:Bristol-Myers Squibb: Employment.