Although there have been tremendous improvements in the management of chronic myelogenous leukemia (CML), the success of treatment is dependent on adherence by the patient to oral tyrosine kinase inhibitor (tki) regimens in unmonitored situations. Little is known about the degree of adherence with tki chemotherapy over prolonged timeframes and the reasons/possible solutions for non-adherence.
Patients (pts) with CML evaluated at the John Theurer Cancer Center having at least one clinic visit since 2010 were identified from the institution’s computerized database. Pts were mailed a 22 item survey designed to elicit opinions regarding adherence with tki therapy. To encourage openness, the survey responses were blinded to the treating physician. A follow-up survey was sent two weeks later.
123 pts were eligible for participation, and 88 returned completed surveys (72% response rate). Respondents were 46 male, 42 female, median age 58, and had a median duration of CML of 65 months (range 4–312). 44 were on first line imatinib, 5 on first line nilotinib, 14 on second line dasatinib, 11 on second line nilotinib, 2 on second line imatinib, 5 on third line tki, 4 on experimental therapies, and 6 status-post transplantation. 81 (92%) of respondents were currently in complete cytogenetic remission, with 19 (22%) having experienced prior cytogenetic relapse and 6 (7%) prior clinical progression. 18% of respondents changed therapies for intolerance and 23% for treatment resistance. There were no statistical differences between respondents and non-respondents based on gender (p=0.50), age (p=0.27), current tki agent (p=0.37), participation on a clinical trial (p=0.61), need for prior change in therapy (p=0.91), or history of disease relapse (p=0.98). In the 100 days prior to the survey, 66 (75%) subjects self-reported taking all their prescribed oral tki’s. However, one quarter (22pts) admitted to missing/skipping doses (most reported missing less than 10 days). Young pts (<50yrs) were less likely to be adherent by self-report (52% vs 85%, p=0.004). Being adherent to current tki therapy could not be predicted by gender (p=0.32), duration since diagnosis (p=0.70), or whether a caregiver was available to assist in medication administration (p=0.75). Participation in a clinical study did not increase adherence (p=1.0 for current participation and p=0.9 for any participation). Neither a history of a change in treatment for any reason (p=0.8) nor a history of change in tki treatment for intolerance vs change for resistance (p=1.0) predicted adherence. Pts who had experienced prior cytogenetic/clinical progression were just as likely to report subsequent non-adherence as those without relapse history (p=0.55). Although the current tki agent (ie, which medication the pt was taking) did not influence adherence in the entire cohort (p=0.12), in the subset of pts on second line therapy the use of dasatinib resulted in higher self-reported adherence compared to second line nilotinib (93% vs 45%, p=0.02). 61% stated that they currently had uncomfortable side-effects, but these pts were as likely to be adherent as those without toxicities (p=1.0). 10% (9pts) admitted to skipping doses due to side-effects without their physician’s knowledge. Among pts whose tki therapy was changed, 22% admitted non-adherence in 100 days preceding the change; which represented a similar rate to the entire cohort. The most commonly stated reasons for non-adherence were forgetfulness (26pts), nausea (9pts), inconvenience (7pts), diarrhea (6pts), and muscle cramps (6pts). 4% self-reported skipping doses due to financial concerns. Methods pts felt that might encourage adherence included improvements in side-effect management (14pts), 3 month prescriptions compared to monthly (12pts), “nothing will help” (9pts), better education (9pts), easier reporting of side-effects (7pts), mail order prescriptions-automatic refills (7pts), and reduced co-payments (7pts).
Adherence with oral tki therapy among pts with CML remains challenging as 25% of our respondents admitted to missing doses; including pts who had been on prolonged therapy (>5yrs) and those pts who had already required treatment changes to second generation agents for resistance/progression. Additional efforts to foster adherence to tki therapy that will allow optimal clinical outcomes are needed.
Goldberg:Novartis Oncology: Honoraria, Speakers Bureau; Bristol Myers Squibb: Honoraria, Speakers Bureau. Off Label Use: Treatments of CML with experimental tyrosine kinase inhibitors, not the focus of the trial. Shah:Novartis Oncology: Speakers Bureau; Bristol Myers Squibb: Speakers Bureau.
Asterisk with author names denotes non-ASH members.