Relationship between achievement of major molecular response or deep molecular response and nilotinib plasma concentration in patients with chronic myeloid leukemia receiving first-line nilotinib therapy.

Abstract

We evaluated the plasma exposure and response relationships of nilotinib for patients with newly diagnosed chronic myeloid leukemia (CML) in real-world practice. For the 26 patients enrolled in this study, at 3, 6, 12, and 24months after nilotinib administration, the trough plasma concentrations (Ctrough) of nilotinib were analyzed. The relationships between nilotinib Ctrough and the molecular response to nilotinib treatment at each point (each n = 26) were evaluated. Median nilotinib Ctrough values were significantly higher in patients with a major molecular response (MMR) at 3months than in patients without an MMR (809 and 420ng/mL, respectively; P = 0.046). Based on the area under the receiver-operating characteristic curve, the threshold value of the nilotinib Ctrough at 3months for predicting MMR achievement was 619ng/mL at the best sensitivity (71.4%) and specificity (77.8%). Patients with a nilotinib Ctrough of above 619ng/mL had a significantly shorter time to achievement of a deep molecular response (DMR; 9.0 and 18.0months, respectively; P = 0.020) and higher rates of DMR by 2years in Kaplan-Meier plots (P = 0.025) compared with that in patients with a nilotinib Ctrough of less than 619ng/mL. For patients with newly diagnosed CML, the nilotinib dose may be adjusted using a Ctrough of above 619ng/mL as the minimum effective concentration, i.e., the lowest concentration required for MMR or DMR achievement within a shorter time, during early stages after beginning therapy to obtain faster and deeper clinical responses.