Dasatinib dose optimisation based on therapeutic drug monitoring reduces pleural effusion rates in chronic myeloid leukaemia patients
Philippe Rousselot
(1, 2, 3, 4, 5)
,
Luigina Mollica
(6)
,
Joelle Guilhot
(7)
,
Agnes Guerci
(8)
,
Franck-Emmanuel Nicolini
(9)
,
Gabriel Etienne
(10)
,
Laurence Legros
(11)
,
Aude Charbonnier
(12)
,
Valerie Coiteux
(13)
,
Caroline Dartigeas
(14)
,
Martine Escoffre-Barbe
(15)
,
Lydia Roy
(16)
,
Pascale Cony-Makhoul
(17)
,
Viviane Dubruille
(18)
,
Martine Gardembas
(19)
,
Francoise Huguet
(20)
,
Delphine Rea
(21, 22)
,
Emilie Cayssials
(7, 23)
,
Francois Guilhot
(7)
,
Anne Bergeron
(22)
,
Mathieu Molimard
(24)
,
Francois-Xavier Mahon
(10, 25)
,
Jean-Michel Cayuela
(21)
,
Lambert Busque
(6)
,
Stephane Bouchet
(26)
1
CHV -
Centre Hospitalier de Versailles André Mignot
2 IDMIT - Infectious Diseases Models for Innovative Therapies
3 CEA - CEA- Saclay
4 UVSQ Santé - Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil
5 IMVA-HB - Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes
6 Hôpital Maisonneuve-Rosemont
7 CIC 1402 - CIC Poitiers – Centre d'investigation clinique de Poitiers
8 CHU Nancy - Centre Hospitalier Universitaire de Nancy
9 Centre Léon Bérard [Lyon]
10 Institut Bergonié [Bordeaux]
11 Hôpital Paul Brousse
12 IPC - Institut Paoli-Calmettes
13 Hôpital Claude Huriez [Lille]
14 CHU Trousseau [Tours]
15 Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Ponchaillou]
16 Hôpital Henri Mondor
17 Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois]
18 CHU Nantes - Centre Hospitalier Universitaire de Nantes = Nantes University Hospital
19 CHU Angers - Centre Hospitalier Universitaire d'Angers
20 IUCT Oncopole - UMR 1037 - Institut Universitaire du Cancer de Toulouse - Oncopole
21 URP_3518 - Recherche clinique appliquée à l'hématologie
22 AP-HP - Hopital Saint-Louis [AP-HP]
23 CHU de Poitiers [La Milétrie] - Centre hospitalier universitaire de Poitiers = Poitiers University Hospital
24 BPH - Bordeaux population health
25 Université de Bordeaux Ségalen [Bordeaux 2]
26 CHU de Bordeaux Pellegrin [Bordeaux]
2 IDMIT - Infectious Diseases Models for Innovative Therapies
3 CEA - CEA- Saclay
4 UVSQ Santé - Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil
5 IMVA-HB - Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes
6 Hôpital Maisonneuve-Rosemont
7 CIC 1402 - CIC Poitiers – Centre d'investigation clinique de Poitiers
8 CHU Nancy - Centre Hospitalier Universitaire de Nancy
9 Centre Léon Bérard [Lyon]
10 Institut Bergonié [Bordeaux]
11 Hôpital Paul Brousse
12 IPC - Institut Paoli-Calmettes
13 Hôpital Claude Huriez [Lille]
14 CHU Trousseau [Tours]
15 Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Ponchaillou]
16 Hôpital Henri Mondor
17 Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois]
18 CHU Nantes - Centre Hospitalier Universitaire de Nantes = Nantes University Hospital
19 CHU Angers - Centre Hospitalier Universitaire d'Angers
20 IUCT Oncopole - UMR 1037 - Institut Universitaire du Cancer de Toulouse - Oncopole
21 URP_3518 - Recherche clinique appliquée à l'hématologie
22 AP-HP - Hopital Saint-Louis [AP-HP]
23 CHU de Poitiers [La Milétrie] - Centre hospitalier universitaire de Poitiers = Poitiers University Hospital
24 BPH - Bordeaux population health
25 Université de Bordeaux Ségalen [Bordeaux 2]
26 CHU de Bordeaux Pellegrin [Bordeaux]
Philippe Rousselot
- Fonction : Auteur
- PersonId : 759734
- ORCID : 0000-0001-6798-7805
Gabriel Etienne
- Fonction : Auteur
- PersonId : 756576
- ORCID : 0000-0001-7600-4954
Mathieu Molimard
- Fonction : Auteur
- PersonId : 760819
- ORCID : 0000-0002-4346-8346
- IdRef : 080590144
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).