Back to Search Start Over

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.

Authors :
Horne GA
Stobo J
Kelly C
Mukhopadhyay A
Latif AL
Dixon-Hughes J
McMahon L
Cony-Makhoul P
Byrne J
Smith G
Koschmieder S
BrÜmmendorf TH
Schafhausen P
Gallipoli P
Thomson F
Cong W
Clark RE
Milojkovic D
Helgason GV
Foroni L
Nicolini FE
Holyoake TL
Copland M
Source :
Leukemia [Leukemia] 2020 Jul; Vol. 34 (7), pp. 1775-1786. Date of Electronic Publication: 2020 Jan 10.
Publication Year :
2020

Abstract

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.

Details

Language :
English
ISSN :
1476-5551
Volume :
34
Issue :
7
Database :
MEDLINE
Journal :
Leukemia
Publication Type :
Academic Journal
Accession number :
31925317
Full Text :
https://doi.org/10.1038/s41375-019-0700-9