Imatinib dose escalation in two patients with chronic myeloid leukemia, with low trough imatinib plasma levels measured at various intervals from the beginning of therapy and with suboptimal treatment response, leads to the achievement of higher plasma levels and major molecular response

• Published in: International journal of hematology 2010-06, Vol.91 (5), p.897-902
• Main Authors: Faber, Edgar, Friedecký, David, Mičová, Kateřina, Divoká, Martina, Katrincsáková, Beata, Rožmanová, Šárka, Jarošová, Marie, Indrák, Karel, Adam, Tomáš
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - administration & dosage; Antineoplastic Agents - blood; Antineoplastic Agents - therapeutic use; Benzamides; Biological and medical sciences; Case Report; Gene Expression Regulation, Leukemic; Hematologic and hematopoietic diseases; Hematology; Humans; Imatinib Mesylate; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - diagnosis; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Medical sciences; Medicine; Medicine & Public Health; Middle Aged; Oncology; Organic Cation Transporter 1 - genetics; Piperazines - administration & dosage; Piperazines - blood; Piperazines - therapeutic use; Pyrimidines - administration & dosage; Pyrimidines - blood; Pyrimidines - therapeutic use; RNA, Messenger - genetics; Treatment Outcome
• ISSN: 0925-5710; 1865-3774
• DOI: 10.1007/s12185-010-0576-y

Despite the prognostic value of trough imatinib plasma levels (IPL) identified in some studies, no recommendations for the use of IPL results in routine management of CML patients have been issued. We report two patients in whom daily imatinib dose was increased from 400 to 600 or 800 mg because of low IPL found at various intervals from the beginning of treatment (7 measurements; mean IPL values = 616.33 and 764.5 ng/mL, respectively). Both patients achieved suboptimal response according to the European LeukemiaNet criteria (complete cytogenetic response was not achieved after 1 year of treatment in patient 1 and major molecular response after 47 months of standard-dose imatinib therapy in patient 2). In addition, we have demonstrated low hOCT - 1 expression at diagnosis in both patients, retrospectively. Escalation of imatinib daily dose resulted in a significant increase of IPL (6 measurements; mean = 1790 and 1416.66 ng/mL, respectively) and in the achievement of complete cytogenetic response in patient 1 after 3 months and major molecular response within 15 and 6 months in both patients. Our cases demonstrate that low IPL identified at various non-predefined intervals from the beginning of therapy may be used for deciding on dose escalation in selected CML patients in the routine clinical setting, especially in cases with suboptimal treatment response.