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|Title:||Nilotinib is associated with a reduced incidence of BCR-ABL mutations vs imatinib in patients with newly diagnosed chronic myeloid leukemia in chronic phase|
De Souza, C.
|Citation:||Blood, 2013; 121(18):3703-3708|
|Publisher:||Amer Soc Hematology|
|Andreas Hochhaus, Giuseppe Saglio, Richard A. Larson, Dong-Wook Kim, Gabriel Etienne, Gianantonio Rosti, Carmino De Souza, Mineo Kurokawa, Matt E. Kalaycio, Albert Hoenekopp, Xiaolin Fan, Yaping Shou, Hagop M. Kantarjian, and Timothy P. Hughes|
|Abstract:||In patients with chronic myeloid leukemia, BCR-ABL mutations contribute to resistance to tyrosine kinase inhibitor therapy. We examined the occurrence of treatment-emergent mutations and their impact on response in patients from the ENESTnd phase 3 trial. At the 3-year data cutoff, mutations were detected in approximately twice as many patients (21) on imatinib 400 mg once daily as on nilotinib (11 patients each on nilotinib 300 mg twice daily and nilotinib 400 mg twice daily). The majority of mutations occurred in patients with intermediate or high Sokal scores. Most mutations (14 [66.7%]) emerging during imatinib treatment were imatinib-resistant and nilotinib-sensitive. Incidence of the T315I mutation was low (found in 3, 2, and 3 patients on nilotinib 300 mg twice daily, nilotinib 400 mg twice daily, and imatinib, respectively) and mostly occurred in patients with high Sokal scores. Of the patients with emergent mutations, 1 of 11, 2 of 11, and 7 of 21 patients on nilotinib 300 mg twice daily, nilotinib 400 mg twice daily, and imatinib, respectively, progressed to accelerated phase/blast crisis (AP/BC) on treatment. Overall, nilotinib led to fewer treatment-emergent BCR-ABL mutations than imatinib and reduced rates of progression to AP/BC in patients with these mutations. (Clinicaltrials.gov NCT00471497).|
|Keywords:||Humans; Blast Crisis; Disease Progression; Benzamides; Piperazines; Pyrimidines; Fusion Proteins, bcr-abl; Antineoplastic Agents; Drug Administration Schedule; Incidence; Follow-Up Studies; Down-Regulation; Dose-Response Relationship, Drug; Gene Frequency; Mutation; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Imatinib Mesylate|
|Rights:||© 2013 by The American Society of Hematology|
|Appears in Collections:||Medicine publications|
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