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Title

Inferior Outcome of Addition of the Aminopeptidase Inhibitor Tosedostat to Standard Intensive Treatment for Elderly Patients with AML and High Risk MDS

Authors
Janssen, Jeroen
Löwenberg, Bob
Manz, Markus
Bargetzi, Mario
Biemond, Bart
Borne, Peter von dem
Breems, Dimitri
Brouwer, Rolf
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Published in Cancers. 2021, vol. 13, no. 4, 672
Abstract Treatment results of AML in elderly patients are unsatisfactory. We hypothesized that addition of tosedostat, an aminopeptidase inhibitor, to intensive chemotherapy may improve outcome in this population. After establishing a safe dose in a run-in phase of the study in 22 patients, 231 eligible patients with AML above 65 years of age (median 70, range 66-81) were randomly assigned in this open label randomized Phase II study to receive standard chemotherapy (3+7) with or without tosedostat at the selected daily dose of 120 mg (n= 116), days 1-21. In the second cycle, patients received cytarabine 1000 mg/m2twice daily on days 1-6 with or without tosedostat. CR/CRi rates in the 2 arms were not significantly different (69% (95% C.I. 60-77%) vs 64% (55-73%), respectively). At 24 months, event-free survival (EFS) was 20% for the standard arm versus 12% for the tosedostat arm (Cox-p = 0.01) and overall survival (OS) 33% vs 18% respectively (p= 0.006). Infectious complications accounted for an increased early death rate in the tosedostat arm. Atrial fibrillation was more common in the tosedostat arm as well. The results of the present study show that the addition of tosedostat to standard chemotherapy does negatively affect the therapeutic outcome of elderly AML patients.
Keywords AMLAminopeptidase inhibitorClinical trialElderlyHigh-risk MDSTosedostat
Identifiers
PMID: 33562393
PMCID: PMC7914531
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Other version: https://www.mdpi.com/2072-6694/13/4/672
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Research group Leucémie et transplantation allogénique de cellules souches hématopoïétiques (982)
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JANSSEN, Jeroen et al. Inferior Outcome of Addition of the Aminopeptidase Inhibitor Tosedostat to Standard Intensive Treatment for Elderly Patients with AML and High Risk MDS. In: Cancers, 2021, vol. 13, n° 4, p. 672. doi: 10.3390/cancers13040672 https://archive-ouverte.unige.ch/unige:159031

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Deposited on : 2022-02-18

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