Response and Adherence to Nilotinib in Daily practice (RAND study): an in-depth observational study of chronic myeloid leukemia patients treated with nilotinib

INTRODUCTION: This comprehensive observational study aimed to gain insight into adherence to nilotinib and the effect of (non)adherence on exposure (C(min)) and treatment outcomes. METHODS: Chronic myeloid leukemia (CML) patients using nilotinib were followed for 12 months. Adherence was measured by Medication Event Monitoring System (MEMS), pill count, and Medication Adherence Report Scale (MARS-5). Nilotinib C(min) and patient-reported outcomes (i.e., quality of life, side effects, beliefs, satisfaction) were measured at baseline, 3, 6, and 12 months. RESULTS: Sixty-eight patients (57.5 ± 15.0 years, 49% female) participated. Median adherence to nilotinib (MEMS and pill count) was ≥ 99% and adherence < 90% was rare. Self-reported nonadherence (MARS-5) increased in the first year of treatment to a third of patients. In line with the strong beliefs in the necessity of taking nilotinib, forgetting to take a dose was more prevalent than intentionally adjusting/skipping doses. Nilotinib C(min) were generally above the therapeutic target in 95% of patients. Patients reported a variety of side effects, of which fatigue was most frequent. The mean C(min) was higher in patients who reported severe itching and fatigue. The overall 1-year MMR rate ranged from 47 to 71%. CONCLUSION: Substantial nonadherence (< 90%) to nilotinib was rare and nilotinib C(min) were generally above the therapeutic target. Lack of response in our group of patients was not related to nonadherence or inadequate C(min). Nevertheless, a considerable number of patients experienced difficulties in adhering to the twice daily fasted dosing regimen, emphasizing the importance of continuous support of medication adherence in CML. CLINICAL TRIAL REGISTRATION: NTR3992 (Netherlands Trial Register, www.trialregister.nl) ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00228-020-02910-3) contains supplementary material, which is available to authorized users.