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

Gillian Horne, Jon Stobo, Caroline Kelly, Arunima Mukhopadhyay, Anne Latif, Judith Dixon, Lynn McMahon, P Cony-Makhoul, Jenny Byrne, Graeme Smith, schafhausen Koschmieder, T BrÜmmendorf , P Schafhausen, P Gallipoli, Fiona Thomson, Wenjuan Cong, R Clark, Dragana Milojkovic, Vignir Helgason, Letizia ForoniFranck-Emmanuel NICOLINI, Tessa Holyoake, Mhairi Copland

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Abstract

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.
Original languageEnglish
Number of pages22
JournalLeukemia
DOIs
Publication statusPublished - 10 Jan 2020

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    Horne, G., Stobo, J., Kelly, C., Mukhopadhyay, A., Latif, A., Dixon, J., McMahon, L., Cony-Makhoul, P., Byrne, J., Smith, G., Koschmieder, S., BrÜmmendorf , T., Schafhausen, P., Gallipoli, P., Thomson, F., Cong, W., Clark, R., Milojkovic, D., Helgason, V., ... Copland, M. (2020). 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. Leukemia. https://doi.org/10.1038/s41375-019-0700-9