Dasatinib dose optimisation based on therapeutic drug monitoring reduces pleural effusion rates in chronic myeloid leukaemia patients - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue British Journal of Haematology Année : 2021

Dasatinib dose optimisation based on therapeutic drug monitoring reduces pleural effusion rates in chronic myeloid leukaemia patients

Gabriel Etienne
Lydia Roy
  • Fonction : Auteur
Mathieu Molimard

Résumé

Dasatinib is a second-generation BCR-ABL1 tyrosine kinase inhibitor approved for patients with chronic myeloid leukaemia (CML). Dasatinib 100 mg per day is associated with an increased risk of pleural effusion (PlEff). We randomly evaluated whether therapeutic drug monitoring (TDM) may reduce dasatinib-associated significant adverse events (AEs) by 12 months (primary endpoint). Eligible patients started dasatinib at 100 mg per day followed by dasatinib (C)min assessment. Patients considered overdosed [(C)min ≥ 3 nmol/l) were randomised between a dose-reduction strategy (TDM arm) and standard of care (control arm). Out of 287 evaluable patients, 80 patients were randomised. The primary endpoint was not met due to early haematological AEs occurring before effective dose reduction. However, a major reduction in the cumulative incidence of PlEff was observed in the TDM arm compared to the control arm (4% vs. 15%; 11% vs. 35% and 12% vs. 39% at one, two and three years, respectively (P = 0·0094)). Molecular responses were superimposable in all arms. Dasatinib TDM during treatment initiation was feasible and resulted in a significant reduction of the incidence of PlEff in the long run, without impairing molecular responses. (NCT01916785; https://clinicaltrials.gov).

Dates et versions

hal-03324903 , version 1 (24-08-2021)

Identifiants

Citer

Philippe Rousselot, Luigina Mollica, Joelle Guilhot, Agnes Guerci, Franck-Emmanuel Nicolini, et al.. Dasatinib dose optimisation based on therapeutic drug monitoring reduces pleural effusion rates in chronic myeloid leukaemia patients. British Journal of Haematology, 2021, 194 (2), pp.393-402. ⟨10.1111/bjh.17654⟩. ⟨hal-03324903⟩
43 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More