title: Minimal cross-intolerance with nilotinib in patients with chronic myeloid leukemia in chronic or accelerated phase who are intolerant to imatinib.
abstract: Nilotinib has significant efficacy in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP) and in patients with CML-CP or CML in accelerated phase (CML-AP) after imatinib failure. We investigated the occurrence of cross-intolerance to nilotinib in imatinib-intolerant patients with CML. Only 1/75 (1%) patients with nonhematologic imatinib intolerance experienced a similar grade 3/4 adverse event (AE), and 3/75 (4%) experienced a similar persistent grade 2 nonhematologic AE on nilotinib. Only 7/40 (18%) patients with hematologic imatinib intolerance discontinued nilotinib, all because of grade 3/4 thrombocytopenia. Ninety percent of imatinib-intolerant patients with CML-CP who did not have complete hematologic response (CHR) at baseline (n = 52) achieved CHR on nilotinib. Nilotinib induced a major cytogenetic response in 66% and 41% of patients with imatinib-intolerant CML-CP and CML-AP (complete cytogenetic response in 51% and 30%), respectively. Minimal cross-intolerance was confirmed in patients with imatinib-intolerant CML. The favorable tolerability of nilotinib in patients with imatinib intolerance leads to alleviation of AE-related symptoms and significant and durable responses. In addition to its established clinical benefit in patients with newly diagnosed CML and those resistant to imatinib, nilotinib is effective and well-tolerated for long-term use in patients with imatinib intolerance. This study is registered at http://www.clinicaltrials.gov as NCT00471497.
authors.affiliation: The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA. Jcortes@mdanderson.org
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Cortes
authors.forename: Andreas
authors.initials: A
authors.lastname: Hochhaus
authors.forename: Philipp D
authors.initials: PD
authors.lastname: le Coutre
authors.forename: Gianantonio
authors.initials: G
authors.lastname: Rosti
authors.forename: Javier
authors.initials: J
authors.lastname: Pinilla-Ibarz
authors.forename: Elias
authors.initials: E
authors.lastname: Jabbour
authors.forename: Kathryn
authors.initials: K
authors.lastname: Gillis
authors.forename: Richard C
authors.initials: RC
authors.lastname: Woodman
authors.forename: Rick E
authors.initials: RE
authors.lastname: Blakesley
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Giles
authors.forename: Hagop M
authors.initials: HM
authors.lastname: Kantarjian
authors.forename: Michele
authors.initials: M
authors.lastname: Baccarani
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001549:Benzamides; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D015465:Leukemia, Myeloid, Accelerated Phase / Q000188:drug therapy* / Q000473:pathology; D015466:Leukemia, Myeloid, Chronic-Phase / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011743:Pyrimidines / Q000627:therapeutic use*; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; C498826:nilotinib