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Master Thesis

Traitement de maintenance par des doses alternées de dasatinib dans la leucémie myéloïde chronique

Abstract : Tyrosine kinase inhibitors (TKIs) induce deep lasting molecular responses in patients with chronic myeloid leukemia (CML). However, 60% of patients eligible to TKIs discontinuation will experience loss of major molecular response (MMR). We evaluated maintenance therapy with dasatinib administrated every other day as an alternative to discontinuation. The main goal of the study was to assess survival without MMR loss (BCR-ABL1IS>0.1%) in maintenance in a retrospective cohort R and then in a prospective trial P. A cohort of 100 patients was studied, including 64 in the R cohort and 36 in the P cohort (inclusion criteria were similar to those of the EUROSKI discontinuation trial that is to say at least 3 years of treatment with TKIs and 1 year of MR4). Median duration of dasatinib was 44.8 (5.6 – 116) and 47.8 (32.7 – 88.4) months with a median daily dose before maintenance of 50 and 100 mg in R and P respectively. With a median follow-up of 24 and 30.7 months in both R and P, the 2-year survival without MMR loss was 80.8% (95% CI, 70.7 – 92.3) and 95.5% (95% CI, 87.1 – 100) respectively. Among the R patients fulfilling the EUROSKI criteria (N=24), this 2-year survival was up to 95% (95% CI, 91 – 100). Patients who lost MMR (N=14) recovered it in 71% cases without detection of resistance mutation. No pleural effusion was recorded in maintenance and patients reported improved quality of life with lower side effects. Maintenance is a feasible alternative to dasatinib discontinuation for patients in 1st or 2nd line treatment with duration of TKIs > or = 3 years and duration of MR4 > or = 1 year.
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Master Thesis
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  • HAL Id : dumas-02293085, version 1

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Clémence Loiseau. Traitement de maintenance par des doses alternées de dasatinib dans la leucémie myéloïde chronique. Médecine humaine et pathologie. 2018. ⟨dumas-02293085⟩

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