Age and Cost Are Associated with Patient Preference for Stopping Tyrosine Kinase Inhibitor Therapy in Chronic Myeloid Leukemia

Background

Tyrosine kinase inhibitors (TKIs) have improved quality of life (QoL) and survival of persons with chronic myeloid leukaemia (CML).  However, therapy is associated with adverse effects and substantial costs, especially in developing countries like China where the local medical insurance partially reimburse TKI therapy.  Consequently, the goal of many persons with CML is achieving treatment-free remission (TFR).  There are few data regarding patient preference for TFR in developing countries.

Aim

Explore therapy goals and patient expectations regarding discontinuing TKI therapy in Chinese with CML and identify variables associated with these preferences.

Methods

Data were collected from May to October, 2014 in an open-label, non-interventional, cross-sectional study using anonymous questionnaires distributed to persons with CML electronically and in print copy.  Questionnaire focused on demographics, CML-related variables before beginning TKI therapy, TKI therapy, response, adverse effects and costs.  Data were also collected on patient treatment goals and willingness to stop TKI.  Before completing the questionnaire patients received general information about CML and CML therapy and were informed about 40% of persons achieving a complete molecular response (CMR) for ≥2 years and stopping TKI therapy remain leukaemia-free for several years and that most of the 60% relapsing after stopping TKI therapy responded to restarting TKI therapy.

Results

1038 questionnaires were collected, 949 of which were evaluable.  888 respondents in chronic phase are included in this analysis.  513 respondents (58%) were male. Median age was 41 years (range, 18–88 years).   663 (75%) respondents were ≤1 year from diagnosis.  750 (84.5%) respondents were on imatinib.  718 (81%) respondents were on branded drugs (non-generic TKIs).  Median TKI treatment duration was 3 years (range, <1–13 years).  666 (75%) and 369 (42%) of respondents reported achieving a complete cytogenetic response (CCyR) and complete molecular response (CMR), respectively.  Most respondents had few adverse effects from TKI therapy.  153 respondents (17%) received TKIs at no cost whilst on clinical trials or through patient assistance programmes (PAPs).  735 respondents (83%) paid part or all of the cost of TKI therapy. Median annual out-of pocket expense was $11,600 (range, $240–$59,600 USD).  430 of 888 respondents (48%) reported TFR, and 401 (45%) reported a normal life span as their treatment goal.  Very few respondents identified preventing disease progression, achieving a CCyR or achieving a CMR as a therapy goal.  734 respondents (83%) expected to discontinue TKI in the future including the 430 respondents who reported TFR as their therapy goal.  The dominant reason for wanting to stop TKI therapy was cost (N=549; 75%) followed by poor QoL from adverse effects of TKI therapy (N=304; 41%), concern regarding long-term adverse effects (N=297; 41%), planned pregnancy (N=103; 14%), disruption in daily life (N=57; 8%) and other reasons (N=37; 5%).   154 respondents (17%) were reluctant or unwilling to stop TKI therapy in the future because they feared disease relapse and/or resistance to TKI therapy (140; 91%).  Multivariate analyses confirmed younger age (HR=0.8; 95% CI, 0.7–0.9; P<0.001; and HR=0.7; 95% CI, 0.6-0.8; P<0.001) and out-of-pocket expense (HR=1.2; 95% CI, 1.1-1.4; P<0.001; and HR=1.5; 95% CI, 1.3-1.8; P<0.001) were associated with TFR as a therapy goal and expectation.  Achieving a CMR (HR=2.0; 95% CI, 1.3-3.3; P=0.003) and decreased QoL from adverse effects (HR=1.2; 95% CI, 1.0-1.5; P=0.029) were independent factors associated with the expectation of discontinuing TKI therapy.

Conclusions

Age and out-of-pocket cost are associated with CML patients’ preference for stopping TKI therapy in China.  This is substantially different from patient attitudes in developed countries.   Expansion of national health insurance coverage and development of generic TKIs are likely to affect this preference.  Our data are important in planning clinical trials of TKI discontinuation in persons with CML.