A randomised evaluation of low-dose cytosine arabinoside (ara-C) plus tosedostat versus low-dose ara-C in older patients with acute myeloid leukaemia: results of the LI-1 trial
Authors
Dennis, MichaelBurnett, A.
Hills, R.
Thomas, I.
Ariti, C.
Severinsen, M. T.
Hemmaway, C.
Greaves, P.
Clark, R. E.
Copland, M
Russell, N.
Affiliation
Department of Haematology, Christie Hospital NHS Trust, ManchesterIssue Date
2021
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Older patients with acute myeloid leukaemia (AML) account for nearly half of those with the disease. Because they are perceived to be unfit for, unwilling to receive, or unlikely to benefit from conventional chemotherapy they represent an important unmet need. Tosedostat is a selective oral aminopeptidase inhibitor, which in phase I/II trials showed acceptable toxicity and encouraging efficacy. We report the only randomised study of low-dose cytosine arabinoside (LDAC) combined with tosedostat (LDAC-T) versus LDAC in untreated older patients not suitable for intensive treatment. A total of 243 patients were randomised 1:1 as part of the 'Pick-a-Winner' LI-1 trial. There was a statistically non-significant increase in the complete remission (CR) rate with the addition of tosedostat, LDAC-T 19% versus LDAC 12% [odds ratio (OR) 0·61, 95% confidence interval (CI) 0·30-1·23; P = 0·17]. For overall response (CR+CR with incomplete recovery of counts), there was little evidence of a benefit to the addition of tosedostat (25% vs. 18%; OR 0·68, 95% CI 0·37-1·27; P = 0·22). However, overall survival (OS) showed no difference (2-year OS 16% vs. 12%, hazard ratio 0·97, 95% CI 0·73-1·28; P = 0·8). Exploratory analyses failed to identify any subgroup benefitting from tosedostat. Despite promising pre-clinical, early non-randomised clinical data with acceptable toxicity and an improvement in response, we did not find evidence that the addition of tosedostat to LDAC produced a survival benefit in this group of patients with AML. International Standard Randomised ControlledCitation
Dennis M, Burnett A, Hills R, Thomas I, Ariti C, Severinsen MT, et al. A randomised evaluation of low-dose cytosine arabinoside (ara-C) plus tosedostat versus low-dose ara-C in older patients with acute myeloid leukaemia: results of the LI-1 trial. Br J Haematol. 2021 May 7.Journal
British Journal of HaematologyDOI
10.1111/bjh.17501PubMed ID
33961292Additional Links
https://dx.doi.org/10.1111/bjh.17501Type
ArticleLanguage
enae974a485f413a2113503eed53cd6c53
10.1111/bjh.17501
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