Nilotinib is associated with a reduced incidence of BCR-ABL mutations vs imatinib in patients with newly diagnosed chronic myeloid leukemia in chronic phase

Simple item page
dc.contributor.authorHochhaus, A.
dc.contributor.authorSaglio, G.
dc.contributor.authorLarson, R.
dc.contributor.authorKim, D.
dc.contributor.authorEtienne, G.
dc.contributor.authorRosti, G.
dc.contributor.authorDe Souza, C.
dc.contributor.authorKurokawa, M.
dc.contributor.authorKalaycio, M.
dc.contributor.authorHoenekopp, A.
dc.contributor.authorFan, X.
dc.contributor.authorShou, Y.
dc.contributor.authorKantarjian, H.
dc.contributor.authorHughes, T.
dc.date.issued2013
dc.description.abstractIn 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).
dc.description.statementofresponsibilityAndreas 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
dc.identifier.citationBlood, 2013; 121(18):3703-3708
dc.identifier.doi10.1182/blood-2012-04-423418
dc.identifier.issn0006-4971
dc.identifier.issn1528-0020
dc.identifier.orcidHughes, T. [0000-0002-0910-3730] [0000-0002-7990-4509]
dc.identifier.urihttp://hdl.handle.net/2440/81418
dc.language.isoen
dc.publisherAmer Soc Hematology
dc.rights© 2013 by The American Society of Hematology
dc.source.urihttps://doi.org/10.1182/blood-2012-04-423418
dc.subjectHumans
dc.subjectBlast Crisis
dc.subjectDisease Progression
dc.subjectBenzamides
dc.subjectPiperazines
dc.subjectPyrimidines
dc.subjectFusion Proteins, bcr-abl
dc.subjectAntineoplastic Agents
dc.subjectDrug Administration Schedule
dc.subjectIncidence
dc.subjectFollow-Up Studies
dc.subjectDown-Regulation
dc.subjectDose-Response Relationship, Drug
dc.subjectGene Frequency
dc.subjectMutation
dc.subjectLeukemia, Myelogenous, Chronic, BCR-ABL Positive
dc.subjectImatinib Mesylate
dc.titleNilotinib is associated with a reduced incidence of BCR-ABL mutations vs imatinib in patients with newly diagnosed chronic myeloid leukemia in chronic phase
dc.typeJournal article
pubs.publication-statusPublished

Files

Collections

Medicine publications