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Objectives: Taking advantage of its food-dependent bioavailability, the present study investigated the effect of a reduced dose taken with real-life meals on the pharmacokinetics (PK) of nilotinib in chronic myeloid leukaemia (CML) patients., Methods: Nilotinib was taken fasted (300 mg BID, days 1-4) or with real-life meals (200 mg BID, days 5-11). Rich sampling (days 1, 3, 8, 11) allowed for non-compartmental PK analysis. Nilotinib exposure (AUC 0-12 h  -C min -C max ) and its intra- and interpatient variability were compared between the two regimens. Adverse events were recorded by means of a patient diary and ECG monitoring., Results: Fifteen patients aged 40-74 years participated. Nilotinib PK following 200 mg BID taken with a meal strongly resembled that of 300 mg BID taken fasted (C min percentile (P)10-P90: 665-1404 ng/mL and 557-1743 ng/mL, respectively). Meals delayed nilotinib absorption. Intra- and interpatient variability were not increased by intake with meals. Nilotinib with food was well tolerated., Conclusion: With support of therapeutic drug monitoring, the use of a reduced 200 mg nilotinib dose with real-life meals seems feasible and safe. Future (confirmatory) studies should further explore the usefulness of nilotinib dosing together with food, including the relationship with treatment efficacy as well as long-term effects on quality of life., Clinical Trial Registration: NTR5000 (Netherlands Trial Register, www.trialregister.nl)., (© 2020 The Authors. European Journal of Haematology published by John Wiley & Sons Ltd.)