Imatinib Meslylate Plasma Levels Predict Compliance in Patients with Chronic Myelogenous Leukemia.

Imatinib mesylate, an inhibitor of the BCR-ABL fusion protein, serves as the current standard of care in the treatment of chronic myeloid leukemia (CML). Since its introduction, significant improvements have been seen in both the course and prognosis of CML. Although imatinib is highly effective in treating CML, recent studies have demonstrated that approximately 30% of patients discontinue imatinib for at least 30 days during their first year of therapy. Clinically, treatment non-adherence is a common reason patients experience suboptimal outcomes and it has therefore become important to establish methods to predict compliance. Based on the association of treatment response with adherence, plasma imatinib levels can be used to predict compliance.

A retrospective analysis was conducted on 19 CML patients (female 5, male 14; median age= 45.3) who received imatinib treatment at LAC+USC Medical Center. Patient charts, laboratory reports and physical examination reports were assessed and plasma concentrations were measured: 1) using liquid chromatography and 2) tandem mass spectrometry. A comparison was then made between Imatinib levels and CCyR. Compliance with imatinib therapy was assessed by chart review and patient history. RESULT: Nineteen patients were analyzed in this study: 1(5%), 17 (90%), and 1 (5%) were treated with 300, 400 and 600 mg imatinib daily, respectively. Fifteen (79%) were Hispanic, 4(21%) were previously treated with interferon, most patients (95%) were in chronic phase when they were diagnosed except one who was in accelerated phase. The median duration of imatinib therapy at the time of plasma imatinib testing was 37 months. The mean and SDs of trough plasma imatinib level was 1362 ng/ml and789 ng/ml, respectively. We found that the imatinib trough concentration was higher in our analysis compared to those reported in the IRIS study and the French group studies, 969 ng/ml and 1058 ng/ml respectively. The patients were divided into two groups (Q1–Q2) based on their imatinib trough level. The average of trough level of the first group (Q1) was 780 ng/ml (±230) (n=9), and that of the second group (Q2) was 1885 ng/ml (±746) (n=10). In total 67% (6 out of 9) of the patients in the first group (Q1) and 20% (2 out of 10) of patients in the second group (Q2) had poor compliance, demonstrating a significantly better compliance in the Q2 (P=0.0001). In terms of their response rate to treatment, Of the 17 patients, a total of 11 achieved a CCyR at 18 months (65%): 63% (5 out of 8) in Q1; 67% (6 out of 9) in Q2. There was no significant correlation between plasma imatinib level and response rate. However, there was a significant correlation between the compliance and the response rate. 80% (8 out of 10) of patients who were adherent to the treatment had CCyR at 18 months, compared to only 43% (3 out of 7) of patients who had CCyR at 18 months in the non-adherent group. (P value=0.0001). Conclusions: Non-adherence to imatinib therapy is common in CML patients and is associated with suboptimal response. Non-compliance should be considered as a possible reason for a patient's poor response to imatinib, prior to considering the patient as imatinib-resistant. Plasma imatinib level can be used as one of the tools to predict compliance. By examining patients' plasma imatinib level, it was shown that high imatinib plasma levels point to a higher likelihood of compliance, and low levels predict a lower likelihood of compliance.

Gorospe:Novartis: Honoraria, Speakers Bureau. Yang:Novartis: Honoraria, Research Funding.