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

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.

Third-line treatment with second-generation tyrosine kinase inhibitors (dasatinib or nilotinib) in patients with chronic myeloid leukemia after two prior TKIs: real-life data on a single center experience along with the review of the literature

“…There were seven studies evaluating the use of 2GTKIs in the third-line setting [11][12][13][14][15][16][17], of which in four of them, patients received both dasatinib and Notes: a These response rates vary according to the disease phase at the start of third-line treatment-please refer to original paper for details. b These percentages were given separately according to disease phase-please refer to original papers for details.…”

“…nilotinib as a third-line therapy [12,13,15,16], whereas in two [11,14], only one 2GTKI (dasatinib and nilotinib, respectively) was administered ( Table 2). In one study, patients received bosutinib in addition to dasatinib and nilotinib as a third-line therapy [17].…”

“…Ribeiro and colleagues evaluated 25 patients with CML who received third-line nilotinib/dasatinib therapy [16]. Nine patients were switched to dasatinib, and 16 patients were switched to nilotinib as a thirdline therapy.…”

“…In addition to that, the choice between these two 2GTKIs is governed mostly by their potential toxicity profiles as well as the comorbidities of the patients [9,10]. Limited data are available, displaying the outcome of CML patients who failed two lines of TKI, and received 2GTKIs as a third-line treatment [11][12][13][14][15][16][17]. The aim of this study is to report our single-center experience on CML patients who received dasatinib or nilotinib as a third-line treatment option, along with a literature review.…”

Expert Opinion on the Treatment of Refractory Chronic Phase Chronic Myeloid Leukaemia

“…20 Treatment with dasatinib or nilotinib in patients with CML (n=25) previously treated with imatinib and a second TKI were evaluated in a single centre study. 19 Of the patients with CP-CML (n=18), 89% achieved a complete haematological response, 13% achieved a complete cytogenic response and 24% achieved a major molecular response. Fifty-six per cent of CP patients lost haematological response with a median of 23 months.…”