PMID- 27133948
OWN - NLM
STAT- MEDLINE
DCOM- 20170418
LR  - 20170930
IS  - 2152-2669 (Electronic)
IS  - 2152-2669 (Linking)
VI  - 16
IP  - 6
DP  - 2016 Jun
TI  - Cross-Intolerance With Dasatinib Among Imatinib-Intolerant Patients With Chronic 
      Phase Chronic Myeloid Leukemia.
PG  - 341-349.e1
LID - S2152-2650(16)30016-7 [pii]
LID - 10.1016/j.clml.2016.03.004 [doi]
AB  - BACKGROUND: 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. PATIENTS AND METHODS: 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. RESULTS: 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). CONCLUSION: Dasatinib could be an 
      appropriate treatment option for imatinib-intolerant patients with CML, with 
      cross-intolerance resulting in discontinuation in a few patients.
CI  - Copyright (c) 2016 Elsevier Inc. All rights reserved.
FAU - Khoury, Hanna J
AU  - Khoury HJ
AD  - Division of Hematology, Department of Hematology and Medical Oncology, Winship 
      Cancer Institute, Emory University, Atlanta, GA. Electronic address: 
      hkhoury@emory.edu.
FAU - Goldberg, Stuart L
AU  - Goldberg SL
AD  - John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, NJ.
FAU - Mauro, Michael J
AU  - Mauro MJ
AD  - Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, 
      NY.
FAU - Stone, Richard M
AU  - Stone RM
AD  - Dana-Farber Cancer Institute, Boston, MA.
FAU - Deininger, Michael W
AU  - Deininger MW
AD  - Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, 
      Salt Lake City, UT.
FAU - Bradley-Garelik, M Brigid
AU  - Bradley-Garelik MB
AD  - Bristol-Myers Squibb, Princeton, NJ.
FAU - Mohamed, Hesham
AU  - Mohamed H
AD  - Bristol-Myers Squibb, Princeton, NJ.
FAU - Guilhot, Francois
AU  - Guilhot F
AD  - Department of Oncology, Hematology, and Cell Therapy, Centre Hospitalier 
      Universitaire de Poitiers, Clinical Investigation Center, Inserm 0802, Poitiers, 
      France.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160329
PL  - United States
TA  - Clin Lymphoma Myeloma Leuk
JT  - Clinical lymphoma, myeloma & leukemia
JID - 101525386
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 8A1O1M485B (Imatinib Mesylate)
RN  - RBZ1571X5H (Dasatinib)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Agents/administration & dosage/*adverse effects/therapeutic use
MH  - Clinical Trials, Phase II as Topic
MH  - Clinical Trials, Phase III as Topic
MH  - Combined Modality Therapy
MH  - Dasatinib/administration & dosage/*adverse effects/therapeutic use
MH  - Female
MH  - Humans
MH  - Imatinib Mesylate/administration & dosage/*adverse effects/therapeutic use
MH  - Kaplan-Meier Estimate
MH  - Leukemia, Myeloid, Chronic-Phase/diagnosis/*drug therapy/mortality
MH  - Male
MH  - Middle Aged
MH  - Protein Kinase Inhibitors/administration & dosage/*adverse effects/therapeutic 
      use
MH  - Retrospective Studies
MH  - Treatment Outcome
MH  - Young Adult
OTO - NOTNLM
OT  - BCR-ABL
OT  - Drug toxicity
OT  - Recurrent adverse event
OT  - Treatment discontinuation
OT  - Tyrosine kinase inhibitor
EDAT- 2016/05/03 06:00
MHDA- 2017/04/19 06:00
CRDT- 2016/05/03 06:00
PHST- 2015/09/14 00:00 [received]
PHST- 2016/03/02 00:00 [revised]
PHST- 2016/03/21 00:00 [accepted]
PHST- 2016/05/03 06:00 [entrez]
PHST- 2016/05/03 06:00 [pubmed]
PHST- 2017/04/19 06:00 [medline]
AID - S2152-2650(16)30016-7 [pii]
AID - 10.1016/j.clml.2016.03.004 [doi]
PST - ppublish
SO  - Clin Lymphoma Myeloma Leuk. 2016 Jun;16(6):341-349.e1. doi: 
      10.1016/j.clml.2016.03.004. Epub 2016 Mar 29.