Display options
Cite
White D, Saunders V, Grigg A, et al. Measurement of in vivo BCR-ABL kinase inhibition to monitor imatinib-induced target blockade and predict response in chronic myeloid leukemia. J Clin Oncol. 2007;25(28):4445-51doi: 10.1200/JCO.2006.09.9499.
White, D., Saunders, V., Grigg, A., Arthur, C., Filshie, R., Leahy, M. F., Lynch, K., To, L. B., & Hughes, T. (2007). Measurement of in vivo BCR-ABL kinase inhibition to monitor imatinib-induced target blockade and predict response in chronic myeloid leukemia. Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 25(28), 4445-51. https://doi.org/10.1200/JCO.2006.09.9499
White, Deborah, et al. "Measurement of in vivo BCR-ABL kinase inhibition to monitor imatinib-induced target blockade and predict response in chronic myeloid leukemia." Journal of clinical oncology : official journal of the American Society of Clinical Oncology vol. 25,28 (2007): 4445-51. doi: https://doi.org/10.1200/JCO.2006.09.9499
White D, Saunders V, Grigg A, Arthur C, Filshie R, Leahy MF, Lynch K, To LB, Hughes T. Measurement of in vivo BCR-ABL kinase inhibition to monitor imatinib-induced target blockade and predict response in chronic myeloid leukemia. J Clin Oncol. 2007 Oct 01;25(28):4445-51. doi: 10.1200/JCO.2006.09.9499. PMID: 17906206.
Copy Download .nbib Format: NLM
Share it on

J Clin Oncol. 2007 Oct 01;25(28):4445-51. doi: 10.1200/JCO.2006.09.9499.

Measurement of in vivo BCR-ABL kinase inhibition to monitor imatinib-induced target blockade and predict response in chronic myeloid leukemia.

Journal of clinical oncology : official journal of the American Society of Clinical Oncology

Deborah White, Verity Saunders, Andrew Grigg, Chris Arthur, Robin Filshie, Michael F Leahy, Kevin Lynch, L Bik To, Timothy Hughes

Affiliations

  1. Division of Hematology, Institute of Medical and Veterinary Science, Adelaide, Australia. [email protected]

PMID: 17906206 DOI: 10.1200/JCO.2006.09.9499

Abstract

PURPOSE: Intrinsic sensitivity to imatinib, based on measurement of inhibitory concentration 50% for imatinib, is variable in untreated patients with chronic myeloid leukemia (CML). This suggests that patient-tailored dosing may be more rational than a fixed dose for all. Dose optimization potentially could be based on accurate measurement of the level of BCR-ABL kinase inhibition achieved in vivo.

PATIENTS AND METHODS: In vivo kinase inhibition was measured by calculating the reduction in protein (p)--Crkl level in mononuclear blood cells taken from 49 CML patients at weekly intervals after imatinib therapy was commenced.

RESULTS: Greater than 50% inhibition (> 50% reduction in p-Crkl from baseline) was achieved by 21% of patients by days 7 to 14 (and maintained in all patients on days 21 to 28) and an additional 24% of patients achieved more than 50% inhibition by days 21 to 28. Thus, overall 45% of patients achieved more than 50% inhibition. All of these patients achieved major molecular responses by 24 months compared with 56% of the patients who failed to achieve 50% kinase inhibition (P < .001). Patients with less than 50% kinase inhibition were also more likely to have suboptimal responses.

CONCLUSION: In vivo BCR-ABL kinase inhibition can be assessed in the first month of imatinib therapy and may provide a valuable guide to optimization of dosage. The extent of BCR-ABL kinase inhibition is an excellent predictor of cytogenetic and molecular response. These observations suggest that dose adjustment based on in vivo measurements of drug-induced target inhibition could be applied in settings beyond imatinib and may be a more effective approach than using one dose for all patients in targeted anticancer therapy.

Substances

MeSH terms

Publication Types