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Mylotarg has potent anti-leukaemic effect : a systematic review and meta-analysis of anti-CD33 antibody treatment in acute myeloid leukaemia
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Loke, Justin, Khan, Josephine N., Wilson, Jayne S., Craddock, Charles and Wheatley, Keith (2015) Mylotarg has potent anti-leukaemic effect : a systematic review and meta-analysis of anti-CD33 antibody treatment in acute myeloid leukaemia. Annals of Hematology , Volume 94 (Number 3). pp. 361-373. doi:10.1007/s00277-014-2218-6 ISSN 0939-5555.
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Official URL: http://dx.doi.org/10.1007/s00277-014-2218-6
Abstract
Conventional chemotherapy is ineffective in the majority of patients with acute myeloid leukaemia (AML), and monoclonal antibodies recognising CD33 expressed on myeloid progenitors (e.g. gemtuzumab ozogamicin (GO)) have been reported to improve outcome in patients with AML. Reports of excess toxicity have resulted in GO’s licence being withdrawn. As a result, the role of these agents remains unclear. A systematic review and meta-analysis included studies of patients with AML who had entered a randomised control trial (RCT), where one arm included anti-CD33 antibody therapy. Fixed effect meta-analysis was used, involving calculation of observed minus expected number of events, and variance for each endpoint in each trial, with the overall treatment effect expressed as Peto’s odds ratio with 95 % confidence interval. Meta-analysis of 11 RCTs with 13 randomisations involving GO was undertaken. Although GO increased induction deaths (p = 0.02), it led to a reduction in resistant disease (p = 0.0009); hence, there was no improvement in complete remission. Whilst GO improved relapse-free survival (hazard ratio (HR) = 0.90, 95 % confidence interval (CI) = 0.84–0.98, p = 0.01), there was no overall benefit of GO in overall survival (OS) (HR = 0.96, 95 % CI = 0.90–1.02, p = 0.2). GO improved OS in patients with favourable cytogenetics, with no evidence of benefit in patients with intermediate or adverse cytogenetics (test for heterogeneity between subtotals p = 0.01). GO has a potent clinically detectable anti-leukaemic effect. Further trials to investigate its optimum delivery and identification of patient populations who may benefit are needed.
Item Type: | Journal Article | ||||||||||
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Subjects: | R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer) | ||||||||||
Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Health Sciences Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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Library of Congress Subject Headings (LCSH): | Antineoplastic agents, Leukemia -- Treatment | ||||||||||
Journal or Publication Title: | Annals of Hematology | ||||||||||
Publisher: | Springer | ||||||||||
ISSN: | 0939-5555 | ||||||||||
Official Date: | March 2015 | ||||||||||
Dates: |
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Volume: | Volume 94 | ||||||||||
Number: | Number 3 | ||||||||||
Number of Pages: | 13 | ||||||||||
Page Range: | pp. 361-373 | ||||||||||
DOI: | 10.1007/s00277-014-2218-6 | ||||||||||
Status: | Peer Reviewed | ||||||||||
Publication Status: | Published | ||||||||||
Access rights to Published version: | Open Access (Creative Commons) | ||||||||||
Date of first compliant deposit: | 29 December 2015 | ||||||||||
Date of first compliant Open Access: | 29 December 2015 | ||||||||||
Funder: | Cancer Research UK (CRUK) |
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