title: Cross-Intolerance With Dasatinib Among Imatinib-Intolerant Patients With Chronic Phase Chronic Myeloid Leukemia.
abstract: BCR-ABL inhibitors have improved the prognosis of patients with chronic myeloid leukemia (CML). However, imatinib, the first approved BCR-ABL inhibitor, must be discontinued in many patients because of resistance or intolerance.
  
  
  
  The present retrospective, pooled analysis of phase II and III data explored the extent of cross-intolerance between imatinib and dasatinib, a second-generation BCR-ABL inhibitor, in 271 CML imatinib-intolerant patients.
  
  
  
  Overall, 47 patients (17%) had cross-intolerance to dasatinib, determined by recurrence of grade 3 or 4 adverse events (AEs). Of the 228 patients who discontinued imatinib because of nonhematologic intolerance, 10 (4%) experienced the same severe nonhematologic AEs with dasatinib, with 4 of these patients (2%) discontinuing dasatinib because of cross-intolerance. Of the 43 patients who discontinued imatinib because of hematologic intolerance, 37 (86%) experienced a recurrence of grade 3 or 4 hematologic AEs with dasatinib, with 8 patients (19%) discontinuing dasatinib because of cross-intolerance. Of the 43 patients taking dasatinib at the optimized dose of 100 mg/d, 1 (2%) discontinued therapy because of recurrence of nonhematologic AEs and 3 (7%) because of recurrence of hematologic AEs. With a median treatment duration of 22 months, the estimated rates of progression-free survival and overall survival at 2 years were greater for patients with nonhematologic versus hematologic intolerance to imatinib who switched to dasatinib (progression-free survival, 94% vs. 68%, respectively; overall survival, 98% vs. 88%, respectively).
  
  
  
  Dasatinib could be an appropriate treatment option for imatinib-intolerant patients with CML, with cross-intolerance resulting in discontinuation in a few patients.
authors.affiliation: Division of Hematology, Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA. Electronic address: hkhoury@emory.edu.
authors.forename: Hanna J
authors.initials: HJ
authors.lastname: Khoury
authors.affiliation: John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, NJ.
authors.forename: Stuart L
authors.initials: SL
authors.lastname: Goldberg
authors.affiliation: Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, NY.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Mauro
authors.affiliation: Dana-Farber Cancer Institute, Boston, MA.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Stone
authors.affiliation: Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Deininger
authors.affiliation: Bristol-Myers Squibb, Princeton, NJ.
authors.forename: M Brigid
authors.initials: MB
authors.lastname: Bradley-Garelik
authors.affiliation: Bristol-Myers Squibb, Princeton, NJ.
authors.forename: Hesham
authors.initials: H
authors.lastname: Mohamed
authors.affiliation: Department of Oncology, Hematology, and Cell Therapy, Centre Hospitalier Universitaire de Poitiers, Clinical Investigation Center, Inserm 0802, Poitiers, France.
authors.forename: François
authors.initials: F
authors.lastname: Guilhot
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D003131:Combined Modality Therapy; D000069439:Dasatinib / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D053208:Kaplan-Meier Estimate; D015466:Leukemia, Myeloid, Chronic-Phase / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D012189:Retrospective Studies; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D000068877:Imatinib Mesylate; D000069439:Dasatinib
keywords: BCR-ABL; Drug toxicity; Recurrent adverse event; Treatment discontinuation; Tyrosine kinase inhibitor