Plasma trough imatinib levels and molecular response in patients of chronic myeloid leukemia (CML): A single institution study from India.

Abstract

7079 Background: One of the reasons proposed for suboptimal responses in Chronic Myeloid Leukemia (CML) patients receiving standard-dose Imatinib has been low blood levels of the drug. Our study aimed to determine the correlation between mean trough Imatinib plasma levels and molecular response in CML chronic phase patients at our centre. We also attempted to compare imatinib plasma levels in patients receiving Gleevec (Novartis) versus patients who were on the generic version of the drug. Methods: One hundred and thirty one (131) CML Chronic phase patients were included in this study. All patients had received 400 mg of imatinib for more than 2 year. Plasma Imatinib trough levels were estimated by high-performance liquid chromatography (HPLC). In order to estimate a threshold for plasma imatinib level that correlates with a favorable response, a receiver operating characteristic (ROC) curve was constructed. Patients were divided into two groups: those with Major Molecular Response (MMR) [bcr/abl : abl ratio <1% as assessed by RQ-PCR] or better (Responders) and those without MMR (bcr/abl : abl ratio =/> 1% as assessed by RQ-PCR) [Non Responders]. Imatinib plasma levels were also compared in patients who were on Gleevec versus those who were on the generic version of the drug. Results: The mean trough imatinib plasma level in the responders was significantly higher (2.10±1.18µg/ml) than in the non responders (1.31±0.72µg/ml) with p value of 0.001. The area under ROC curve was 0.733, with best sensitivity (51.85%) and specificity (89.42%) at a plasma threshold of 0.988 µg/ml. There was no significant difference between the mean trough plasma imatinib levels of the patients who were on Gleevec as compared to those who were on generic Imatinib (p value > 0.05). Conclusions: Plasma Imatinib trough levels were statistically similar in the Gleevec and generic Imatinib groups. These levels showed a statistically significant correlation with molecular response. Trough plasma imatinib levels may be a marker for suboptimal response to Imatinib and may identify patients in whom increase of drug dose or change to second generation tyrosine kinase inhibitors may be indicated.