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).
journal_name
Bloodjournal_title
Bloodauthors
Hochhaus A,Saglio G,Larson RA,Kim DW,Etienne G,Rosti G,De Souza C,Kurokawa M,Kalaycio ME,Hoenekopp A,Fan X,Shou Y,Kantarjian HM,Hughes TPdoi
10.1182/blood-2012-04-423418subject
Has Abstractpub_date
2013-05-02 00:00:00pages
3703-8issue
18eissn
0006-4971issn
1528-0020pii
blood-2012-04-423418journal_volume
121pub_type
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