Outcome After Failure of Second Generation Tyrosine Kinase Inhibitors Treatment As First-line Therapy for Patients With Chronic Myeloid Leukemia

For the first time, 40 patients with chronic myeloid leukemia (CML) in chronic phase (CP) or accelerated phase (AP) in whom second-generation (2G) tyrosine kinase inhibitors (TKIs) failed as first-line therapy among 217 patients were evaluated in a retrospective analysis to determine their outcome. Toxicity and patient preference were the main reasons of treatment discontinuation and there was good response to alternative TKIs afterward. Introduction: The outcome of patients with CML who discontinue 2G-TKI initial therapy is unknown. We analyzed the characteristics of patients in whom treatment with first-line 2G-TKIs had failed. Patients and Methods: A total of 218 patients with CML were treated with dasatinib (n = 101) or nilotinib (n = 117; 12 in AP). After a median follow-up of 23 months, 40 patients (18%) discontinued therapy: 25 initially treated with nilotinib (21% of all treated with nilotinib; 6 treated in AP) and 15 (15%) initially treated with dasatinib. Median age of the patients was 47 (range, 19-79) years, and they had received therapy for a median of 8 (range, 0-62) months. Results: Reasons for treatment discontinuation include: toxicity, 16 patients; resistance in CP, 5 patients; transformation to blast phase, 4 patients (2 treated in AP); and other reasons, 15 patients. Subsequent treatment was imatinib in 11 patients, nilotinib in 7, dasatinib in 4, ponatinib in 2, chemotherapy plus dasatinib in 3, stem cell transplant in 2, bafetinib in 1, and unknown or none in 8 patients. A complete cytogenetic response was achieved in 19 patients, including 17 with major molecular response. Fourteen of the patients who achieved a complete molecular response or major molecular response with subsequent TKIs were in CP at the time of 2G-TKI discontinuation. Conclusion: We conclude that treatment failure after first-line therapy with 2G-TKIs is mostly associated with toxicity or patient preference, and these patients respond well to alternative TKIs. (C) 2013 Elsevier Inc. All rights reserved.