PMID- 32366938
OWN - NLM
STAT- MEDLINE
DCOM- 20201007
LR  - 20240328
IS  - 1476-5551 (Electronic)
IS  - 0887-6924 (Print)
IS  - 0887-6924 (Linking)
VI  - 34
IP  - 6
DP  - 2020 Jun
TI  - Expert opinion-management of chronic myeloid leukemia after resistance to 
      second-generation tyrosine kinase inhibitors.
PG  - 1495-1502
LID - 10.1038/s41375-020-0842-9 [doi]
AB  - Regardless of line of therapy, treatment goals in chronic phase chronic myeloid 
      leukemia (CML) are: avoid progression to accelerated phase or blast crisis CML 
      such that patients achieve a life expectancy comparable with that of the general 
      population; avoid adverse events (AEs); and restore and maintain quality of life. 
      The most important prognostic factor for achieving these goals is response to 
      tyrosine kinase inhibitors (TKIs) at key milestones. For patients failing a TKI, 
      a treatment change is mandatory to limit the risk of progression and death. There 
      is currently no precise guideline for patients that fail a second-generation TKI, 
      and there is a paucity of data to guide clinical decision making in this setting. 
      There is, therefore, an unmet need for practical and actionable guidance on how 
      to manage patients who fail a second-generation TKI. Although the term 'failure' 
      includes patients failing for resistance or intolerance, the focus of this paper 
      is failure of a second-generation TKI because of resistance. CML patients who 
      fail their first second-generation TKI for true resistance need a more potent 
      therapy. In these patients, the key issues to consider are the relative 
      appropriateness of early allogeneic hematopoietic stem cell transplantation or 
      the use of a further TKI. Selection of the next line of treatment after 
      second-generation TKI resistance should be individualized and must be based on 
      patient-specific factors including cytogenetics, mutation profile, comorbidities, 
      age, previous history of AEs with prior TKI therapy, and risk profile for AEs on 
      specific TKIs. This expert opinion paper is not in conflict with existing 
      recommendations, but instead represents an evolution of previous notions, based 
      on new data, insights, and clinical experience. We review the treatment options 
      for patients resistant to second-generation TKI therapy and provide our clinical 
      opinions and guidance on key considerations for treatment decision making.
FAU - Hochhaus, Andreas
AU  - Hochhaus A
AD  - Klinik fur Innere Medizin II, Universitatsklinikum Jena, Jena, Germany. 
      andreas.hochhaus@med.uni-jena.de.
FAU - Breccia, Massimo
AU  - Breccia M
AD  - Sapienza University of Rome, Rome, Italy.
FAU - Saglio, Giuseppe
AU  - Saglio G
AD  - University of Turin, Turin, Italy.
FAU - Garcia-Gutierrez, Valentin
AU  - Garcia-Gutierrez V
AD  - Hospital Universitario Ramon y Cajal (IRYCIS), Madrid, Spain.
FAU - Rea, Delphine
AU  - Rea D
AD  - Hopital St. Louis, Paris, France.
FAU - Janssen, Jeroen
AU  - Janssen J
AD  - Department of Hematology, Cancer Center Amsterdam, Amsterdam University Medical 
      Centers, loc. VUMC, Amsterdam, The Netherlands.
FAU - Apperley, Jane
AU  - Apperley J
AD  - Hammersmith Hospital, Imperial College London, London, UK.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20200504
PL  - England
TA  - Leukemia
JT  - Leukemia
JID - 8704895
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Protein Kinase Inhibitors)
SB  - IM
MH  - Antineoplastic Agents/therapeutic use
MH  - *Drug Resistance, Neoplasm
MH  - Humans
MH  - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/*therapy
MH  - Protein Kinase Inhibitors/therapeutic use
PMC - PMC7266739
COIS- Members of the expert panel declare the following potential conflicts of 
      interest: AH, Research support: BMS, Incyte, MSD, Novartis, Pfizer. Honoraria: 
      BMS, Fusion Pharma, Incyte, Novartis, Pfizer, Takeda. MB, Honoraria: Celgene, 
      Incyte, Novartis, Pfizer. GS, No financial relationship to disclose. VGG, 
      Research support: BMS, Incyte, Novartis, Pfizer. Honoraria: BMS, Incyte, 
      Novartis, Pfizer. DR, Honoraria: BMS, Novartis, Pfizer, Incyte. JJ, Research 
      support: Novartis, BMS; Honoraria: Pfizer, Novartis, Incyte, Abbvie; Founder of 
      Apps for Care and Science Foundation, developer of the HematologyApp. This 
      non-profit organization is supported by Amgen, Sanofi-Genzyme, Takeda, Jazz, 
      Roche, Servier, Celgene, Daiichi-Sankyo, Janssen, Incyte and BMS. JFA, Research 
      support: Incyte, Novartis, Pfizer. Honoraria: BMS, Incyte, Novartis, Pfizer. None 
      of the authors received an honorarium for this specific work.
EDAT- 2020/05/06 06:00
MHDA- 2020/10/08 06:00
PMCR- 2020/05/04
CRDT- 2020/05/06 06:00
PHST- 2020/04/09 00:00 [received]
PHST- 2020/04/16 00:00 [accepted]
PHST- 2020/04/16 00:00 [revised]
PHST- 2020/05/06 06:00 [pubmed]
PHST- 2020/10/08 06:00 [medline]
PHST- 2020/05/06 06:00 [entrez]
PHST- 2020/05/04 00:00 [pmc-release]
AID - 10.1038/s41375-020-0842-9 [pii]
AID - 842 [pii]
AID - 10.1038/s41375-020-0842-9 [doi]
PST - ppublish
SO  - Leukemia. 2020 Jun;34(6):1495-1502. doi: 10.1038/s41375-020-0842-9. Epub 2020 May 
      4.