A randomised phase II trial of hydroxychloroquine and imatinib versus imatinib alone for patients with chronic myeloid leukaemia in major cytogenetic response with residual disease.
Aged
Antineoplastic Combined Chemotherapy Protocols
/ therapeutic use
Cytogenetic Analysis
/ methods
Female
Follow-Up Studies
Fusion Proteins, bcr-abl
/ genetics
Humans
Hydroxychloroquine
/ administration & dosage
Imatinib Mesylate
/ administration & dosage
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
/ drug therapy
Male
Middle Aged
Prognosis
Retrospective Studies
Survival Rate
Journal
Leukemia
ISSN: 1476-5551
Titre abrégé: Leukemia
Pays: England
ID NLM: 8704895
Informations de publication
Date de publication:
07 2020
07 2020
Historique:
received:
08
08
2019
accepted:
24
12
2019
revised:
23
12
2019
pubmed:
12
1
2020
medline:
28
10
2020
entrez:
12
1
2020
Statut:
ppublish
Résumé
In chronic-phase chronic myeloid leukaemia (CP-CML), residual BCR-ABL1+ leukaemia stem cells are responsible for disease persistence despite TKI. Based on in vitro data, CHOICES (CHlorOquine and Imatinib Combination to Eliminate Stem cells) was an international, randomised phase II trial designed to study the safety and efficacy of imatinib (IM) and hydroxychloroquine (HCQ) compared with IM alone in CP-CML patients in major cytogenetic remission with residual disease detectable by qPCR. Sixty-two patients were randomly assigned to either arm. Treatment 'successes' was the primary end point, defined as ≥0.5 log reduction in 12-month qPCR level from trial entry. Selected secondary study end points were 24-month treatment 'successes', molecular response and progression at 12 and 24 months, comparison of IM levels, and achievement of blood HCQ levels >2000 ng/ml. At 12 months, there was no difference in 'success' rate (p = 0.58); MMR was achieved in 80% (IM) vs 92% (IM/HCQ) (p = 0.21). At 24 months, the 'success' rate was 20.8% higher with IM/HCQ (p = 0.059). No patients progressed. Seventeen serious adverse events, including four serious adverse reactions, were reported; diarrhoea occurred more frequently with combination. IM/HCQ is tolerable in CP-CML, with modest improvement in qPCR levels at 12 and 24 months, suggesting autophagy inhibition maybe of clinical value in CP-CML.
Identifiants
pubmed: 31925317
doi: 10.1038/s41375-019-0700-9
pii: 10.1038/s41375-019-0700-9
pmc: PMC7224085
mid: EMS85323
doi:
Substances chimiques
Hydroxychloroquine
4QWG6N8QKH
Imatinib Mesylate
8A1O1M485B
Fusion Proteins, bcr-abl
EC 2.7.10.2
Types de publication
Clinical Trial, Phase II
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1775-1786Subventions
Organisme : Medical Research Council
ID : G0900882
Pays : United Kingdom
Organisme : Medical Research Council
ID : G1000288
Pays : United Kingdom
Organisme : Cancer Research UK
Pays : United Kingdom
Organisme : Chief Scientist Office
Pays : United Kingdom
Commentaires et corrections
Type : CommentIn
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