Treatment with dasatinib or nilotinib in chronic myeloid leukemia patients who failed to respond to two previously administered tyrosine kinase inhibitors - a single center experience

Authors

  • Beatriz Felicio Ribeiro Universidade de Campinas; Centro de Hematologia e Hemoterapia; Universidade Estadual de Campinas
  • Eliana C.M. Miranda Universidade de Campinas; Centro de Hematologia e Hemoterapia; Universidade Estadual de Campinas
  • Dulcinéia Martins de Albuquerque Universidade de Campinas; Centro de Hematologia e Hemoterapia; Universidade Estadual de Campinas
  • Márcia T. Delamain Universidade de Campinas; Centro de Hematologia e Hemoterapia; Universidade Estadual de Campinas
  • Gislaine Oliveira-Duarte Universidade de Campinas; Centro de Hematologia e Hemoterapia; Universidade Estadual de Campinas
  • Maria Helena Almeida Universidade de Campinas; Centro de Hematologia e Hemoterapia; Universidade Estadual de Campinas
  • Bruna Vergílio Universidade de Campinas; Centro de Hematologia e Hemoterapia; Universidade Estadual de Campinas
  • Rosana Antunes da Silveira Universidade de Campinas; Centro de Hematologia e Hemoterapia; Universidade Estadual de Campinas
  • Vagner Oliveira-Duarte Universidade de Campinas; Centro de Hematologia e Hemoterapia; Universidade Estadual de Campinas
  • Irene Lorand-Metze Universidade de Campinas; Centro de Hematologia e Hemoterapia; Universidade Estadual de Campinas
  • Carmino A. De Souza Universidade de Campinas; Centro de Hematologia e Hemoterapia; Universidade Estadual de Campinas
  • Katia B.B. Pagnano Universidade de Campinas; Centro de Hematologia e Hemoterapia; Universidade Estadual de Campinas

DOI:

https://doi.org/10.6061/clinics/2015(08)04

Abstract

OBJECTIVE: To evaluate hematological, cytogenetic and molecular responses as well as the overall, progression-free and event-free survivals of chronic myeloid leukemia patients treated with a third tyrosine kinase inhibitor after failing to respond to imatinib and nilotinib/dasatinib. METHODS: Bone marrow karyotyping and real-time quantitative polymerase chain reaction were performed at baseline and at 3, 6, 12 and 18 months after the initiation of treatment with a third tyrosine kinase inhibitor. Hematologic, cytogenetic and molecular responses were defined according to the European LeukemiaNet recommendations. BCR-ABL1 mutations were analyzed by Sanger sequencing. RESULTS: We evaluated 25 chronic myeloid leukemia patients who had been previously treated with imatinib and a second tyrosine kinase inhibitor. Nine patients were switched to dasatinib, and 16 patients were switched to nilotinib as a third-line therapy. Of the chronic phase patients (n=18), 89% achieved a complete hematologic response, 13% achieved a complete cytogenetic response and 24% achieved a major molecular response. The following BCR-ABL1 mutations were detected in 6/14 (43%) chronic phase patients: E255V, Y253H, M244V, F317L (2) and F359V. M351T mutation was found in one patient in the accelerated phase of the disease. The five-year overall, progression-free and event-free survivals were 86, 54 and 22% (p<0.0001), respectively, for chronic phase patients and 66%, 66% and 0% (p<0.0001), respectively, for accelerated phase patients. All blast crisis patients died within 6 months of treatment. Fifty-six percent of the chronic phase patients lost their hematologic response within a median of 23 months. CONCLUSIONS: Although the responses achieved by the third tyrosine kinase inhibitor were not sustainable, a third tyrosine kinase inhibitor may be an option for improving patient status until a donor becomes available for transplant. Because the long-term outcome for these patients is poor, the development of new therapies for resistant chronic myeloid leukemia patients is necessary.

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Published

2015-08-01

Issue

Section

Clinical Sciences

How to Cite

Ribeiro, B. F., Miranda, E. C., Albuquerque, D. M. de, Delamain, M. T., Oliveira-Duarte, G., Almeida, M. H., Vergílio, B., Silveira, R. A. da, Oliveira-Duarte, V., Lorand-Metze, I., Souza, C. A. D., & Pagnano, K. B. (2015). Treatment with dasatinib or nilotinib in chronic myeloid leukemia patients who failed to respond to two previously administered tyrosine kinase inhibitors - a single center experience . Clinics, 70(8), 550-555. https://doi.org/10.6061/clinics/2015(08)04