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

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.

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.

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%.

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.

NTR3992 (Netherlands Trial Register, www.trialregister.nl ).