TY - JOUR
T1 - 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
AU - Horne, Gillian
AU - Stobo, Jon
AU - Kelly, Caroline
AU - Mukhopadhyay, Arunima
AU - Latif, Anne
AU - Dixon, Judith
AU - McMahon, Lynn
AU - Cony-Makhoul, P
AU - Byrne, Jenny
AU - Smith, Graeme
AU - Koschmieder, schafhausen
AU - BrÜmmendorf , T
AU - Schafhausen, P
AU - Gallipoli, P
AU - Thomson, Fiona
AU - Cong, Wenjuan
AU - Clark, R
AU - Milojkovic, Dragana
AU - Helgason, Vignir
AU - Foroni, Letizia
AU - NICOLINI, Franck-Emmanuel
AU - Holyoake, Tessa
AU - Copland, Mhairi
PY - 2020/1/10
Y1 - 2020/1/10
N2 - Abstract: 1
In chronic-phase chronic myeloid leukaemia (CP-CML), residual BCR-ABL1+ leukaemia stem cells are 2
responsible for disease persistence despite TKI. Based on in vitro data, CHOICES (CHlorOquine and 3
Imatinib Combination to Eliminate Stem cells) was an international, randomised phase II trial designed 4
to study the safety and efficacy of imatinib (IM) and hydroxychloroquine (HCQ) compared to IM alone in 5
CP-CML patients in major cytogenetic remission with residual disease detectable by qPCR. Sixty-two 6
patients were randomly assigned to either arm. Treatment ‘successes’ was the primary end-point, 7
defined as ≥0.5 log reduction in 12-month qPCR level from trial entry. Selected secondary study end-8
points were 24-month treatment ‘successes’, molecular response and progression at 12 and 24 months, 9
comparison of IM levels, and achievement of blood HCQ levels >2000ng/ml. At 12 months, there was no 10
difference in ‘success’ rate (p=0.58); MMR was achieved in 80% (IM) vs 92% (IM/HCQ) (p=0.21). At 24 11
months, the ‘success’ rate was 20.8% higher with IM/HCQ (p=0.059). No patients progressed. 12
Seventeen adverse events, including four serious adverse reactions, were reported; diarrhoea occurred 13
more frequently with combination. IM/HCQ is tolerable in CP-CML, with modest improvement in qPCR 14
levels at 12 and 24 months, suggesting autophagy inhibition maybe of clinical value in CP-CML.
AB - Abstract: 1
In chronic-phase chronic myeloid leukaemia (CP-CML), residual BCR-ABL1+ leukaemia stem cells are 2
responsible for disease persistence despite TKI. Based on in vitro data, CHOICES (CHlorOquine and 3
Imatinib Combination to Eliminate Stem cells) was an international, randomised phase II trial designed 4
to study the safety and efficacy of imatinib (IM) and hydroxychloroquine (HCQ) compared to IM alone in 5
CP-CML patients in major cytogenetic remission with residual disease detectable by qPCR. Sixty-two 6
patients were randomly assigned to either arm. Treatment ‘successes’ was the primary end-point, 7
defined as ≥0.5 log reduction in 12-month qPCR level from trial entry. Selected secondary study end-8
points were 24-month treatment ‘successes’, molecular response and progression at 12 and 24 months, 9
comparison of IM levels, and achievement of blood HCQ levels >2000ng/ml. At 12 months, there was no 10
difference in ‘success’ rate (p=0.58); MMR was achieved in 80% (IM) vs 92% (IM/HCQ) (p=0.21). At 24 11
months, the ‘success’ rate was 20.8% higher with IM/HCQ (p=0.059). No patients progressed. 12
Seventeen adverse events, including four serious adverse reactions, were reported; diarrhoea occurred 13
more frequently with combination. IM/HCQ is tolerable in CP-CML, with modest improvement in qPCR 14
levels at 12 and 24 months, suggesting autophagy inhibition maybe of clinical value in CP-CML.
U2 - 10.1038/s41375-019-0700-9
DO - 10.1038/s41375-019-0700-9
M3 - Article (Academic Journal)
C2 - 31925317
SN - 0887-6924
JO - Leukemia
JF - Leukemia
ER -