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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.
- 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.
- Subjects :
- Aged
Female
Follow-Up Studies
Humans
Hydroxychloroquine administration & dosage
Imatinib Mesylate administration & dosage
Leukemia, Myelogenous, Chronic, BCR-ABL Positive genetics
Leukemia, Myelogenous, Chronic, BCR-ABL Positive pathology
Male
Middle Aged
Prognosis
Retrospective Studies
Survival Rate
Antineoplastic Combined Chemotherapy Protocols therapeutic use
Cytogenetic Analysis methods
Fusion Proteins, bcr-abl genetics
Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy
Subjects
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