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Rousselot P, Mollica L, Guilhot J, et al. Dasatinib dose optimisation based on therapeutic drug monitoring reduces pleural effusion rates in chronic myeloid leukaemia patients. Br J Haematol. 2021;194(2):393-402doi: 10.1111/bjh.17654.
Rousselot, P., Mollica, L., Guilhot, J., Guerci, A., Nicolini, F. E., Etienne, G., Legros, L., Charbonnier, A., Coiteux, V., Dartigeas, C., Escoffre-Barbe, M., Roy, L., Cony-Makhoul, P., Dubruille, V., Gardembas, M., Huguet, F., Réa, D., Cayssials, E., Guilhot, F., Bergeron, A., Molimard, M., Mahon, F. X., Cayuela, J. M., Busque, L., & Bouchet, S. (2021). Dasatinib dose optimisation based on therapeutic drug monitoring reduces pleural effusion rates in chronic myeloid leukaemia patients. British journal of haematology, 194(2), 393-402. https://doi.org/10.1111/bjh.17654
Rousselot, Philippe, et al. "Dasatinib dose optimisation based on therapeutic drug monitoring reduces pleural effusion rates in chronic myeloid leukaemia patients." British journal of haematology vol. 194,2 (2021): 393-402. doi: https://doi.org/10.1111/bjh.17654
Rousselot P, Mollica L, Guilhot J, Guerci A, Nicolini FE, Etienne G, Legros L, Charbonnier A, Coiteux V, Dartigeas C, Escoffre-Barbe M, Roy L, Cony-Makhoul P, Dubruille V, Gardembas M, Huguet F, Réa D, Cayssials E, Guilhot F, Bergeron A, Molimard M, Mahon FX, Cayuela JM, Busque L, Bouchet S. Dasatinib dose optimisation based on therapeutic drug monitoring reduces pleural effusion rates in chronic myeloid leukaemia patients. Br J Haematol. 2021 Jul;194(2):393-402. doi: 10.1111/bjh.17654. Epub 2021 Jun 30. PMID: 34195988.
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Br J Haematol. 2021 Jul;194(2):393-402. doi: 10.1111/bjh.17654. Epub 2021 Jun 30.

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

British journal of haematology

Philippe Rousselot, Luigina Mollica, Joëlle Guilhot, Agnès Guerci, Franck E Nicolini, Gabriel Etienne, Laurence Legros, Aude Charbonnier, Valérie Coiteux, Caroline Dartigeas, Martine Escoffre-Barbe, Lydia Roy, Pascale Cony-Makhoul, Viviane Dubruille, Martine Gardembas, Françoise Huguet, Delphine Réa, Emilie Cayssials, François Guilhot, Anne Bergeron, Mathieu Molimard, Francois-Xavier Mahon, Jean-Michel Cayuela, Lambert Busque, Stéphane Bouchet

Affiliations

  1. Department of Hematology and Oncology, Centre Hospitalier de Versailles, Le Chesnay, France.
  2. UMR1184, IDMIT Department Université Paris-Saclay, Commissariat à l'énergie atomique et aux énergies alternatives, University of Versailles Saint-Quentin-en-Yvelines, Montigny-Le-Bretonneux, France.
  3. Department of Hematology, Hôpital Maisonneuve-Rosemont, University of Montréal, Montréal, Québec, Canada.
  4. Inserm CIC 1402 CHU de Poitiers, Poitiers, France.
  5. Department of Hematology, CHU Brabois Vandoeuvre, Nancy, France.
  6. Department of Hematology, Centre Léon Bérard, Lyon, France.
  7. Department of Hematology, Institut Bergonié, Bordeaux, France.
  8. Department of Hematology, Hôpital Paul Brousse, Villejuif, France.
  9. Department of Hematology, Institut Paoli Calmette, Marseille, France.
  10. Department of Hematology, Hôpital Huriez - CHRU, Lille, France.
  11. Department of Hematology, CHU de Tours, Tours, France.
  12. Department of Hematology, Centre Hospitalier Pontchaillou, Rennes, France.
  13. Department of Hematology, Hôpital Henri Mondor, AP-HP, Créteil, France.
  14. Department of Hematology, Centre Hospitalier Annecy Genevois, Pringy, France.
  15. Department of Hematology, Hôpital Hôtel-Dieu, CHU de Nantes, Nantes, France.
  16. Department of Hematology, CHU d'Angers, Angers, France.
  17. Department of Hematology, Institut Universitaire du Cancer - Oncopole, Toulouse, France.
  18. Department of Hematology, Hôpital Saint-Louis et EA3518, AP-HP, Paris, France.
  19. Department of Hematology, CHU de Poitiers, Poitiers, France.
  20. Department of Pneumology, Hôpital Saint-Louis, AP-HP, Paris, France.
  21. Clinical Pharmacology Department, Centre Hospitalier Pellegrin, CHU de Bordeaux, Bordeaux, France.
  22. University of Bordeaux Ségalen, Bordeaux, France.
  23. Hematology and Molecular Biology and EA3518, Hôpital Saint-Louis, AP-HP, Paris, France.

PMID: 34195988 DOI: 10.1111/bjh.17654

Abstract

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).

© 2021 British Society for Haematology and John Wiley & Sons Ltd.

Keywords: chronic leukaemia; pharmacology; tyrosine kinases

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