Imatinib Optimized Therapy Improves Major Molecular Response Rates in Patients with Chronic Myeloid Leukemia.

Autor: Johnson-Ansah H; Department of Hematology, CHU Côte de Nacre, 14000 Caen, France., Maneglier B; Pharmacology Department, Centre Hospitalier de Versailles, 78150 Le Chesnay, France., Huguet F; Department of Hematology, CHU, Institut Universitaire du Cancer-Oncopole, 31100 Toulouse, France., Legros L; Department of Hematology, Hôpital Bicêtre AP-HP, 94270 Bicêtre, France., Escoffre-Barbe M; Department of Hematology, Centre Hospitalier Pontchaillou, 35000 Rennes, France., Gardembas M; Department of Hematology, CHU d'Angers, 49100 Angers, France., Cony-Makhoul P; Department of Hematology, Centre Hospitalier Annecy Genevois, 74370 Pringy, France., Coiteux V; Department of Hematology, Hôpital Huriez-CHRU, 59000 Lille, France., Sutton L; Department of Hematology, Hôpital Victor Dupouy, 95107 Argenteuil, France., Abarah W; Department of Hematology, Hôpital de Meaux, 77100 Meaux, France., Pouaty C; Department of Hematology, Centre Hospitalier de Dieppe, 76202 Dieppe, France., Pignon JM; Department of Hematology, Hôpital de Dunkerque, 59240 Dunkerque, France., Choufi B; Department of Hematology, Hôpital de Boulogne, 62200 Boulogne, France., Visanica S; Department of Hematology, Hôpital Notre Dame de Bon Secours, 57000 Metz, France., Deau B; Department of Hematology, Hôpital Cochin APHP, 75014 Paris, France., Morisset L; Research Department, Centre Hospitalier de Versailles, 78150 Le Chesnay, France., Cayssials E; Inserm CIC 802, CHU de Poitiers, 86000 Poitiers, France., Molimard M; Department of Pharmacology, Centre Hospitalier Pellegrin-Tripode, 33000 Bordeaux, France., Bouchet S; Department of Pharmacology, Centre Hospitalier Pellegrin-Tripode, 33000 Bordeaux, France., Mahon FX; Department of Hematology, Institut Bergonié, 33076 Bordeaux, France., Nicolini F; Department of Hematology, Centre Léon Bérard, 69008 Lyon, France., Aegerter P; Unité de Recherche Clinique et Département de Santé Publique, GIRCI Ile de France, Hôpital Ambroise Paré, 92100 Boulogne, France., Cayuela JM; Hematology and Molecular Biology and EA3518, Hôpital Saint-Louis, AP-HP, 75010 Paris, France., Delord M; Research Department, Centre Hospitalier de Versailles, 78150 Le Chesnay, France., Bruzzoni-Giovanelli H; Hôpital Saint-Louis, AP-HP/INSERM, Université Paris-Cité et CIC 1427, 75010 Paris, France., Rousselot P; Department of Hematology, Centre Hospitalier de Versailles, 78157 Le Chesnay, France.; UMR1184, IDMIT Department, Commissariat à L'énergie Atomique et aux Energies Alternatives, University of Versailles Saint-Quentin-en-Yvelines Paris-Saclay, 92265 Fontenay-Aux-Roses, France.
Jazyk: angličtina
Zdroj: Pharmaceutics [Pharmaceutics] 2022 Aug 12; Vol. 14 (8). Date of Electronic Publication: 2022 Aug 12.
DOI: 10.3390/pharmaceutics14081676
Abstrakt: The registered dose for imatinib is 400 mg/d, despite high inter-patient variability in imatinib plasmatic exposure. Therapeutic drug monitoring (TDM) is routinely used to maximize a drug’s efficacy or tolerance. We decided to conduct a prospective randomized trial (OPTIM-imatinib trial) to assess the value of TDM in patients with chronic phase chronic myelogenous treated with imatinib as first-line therapy (NCT02896842). Eligible patients started imatinib at 400 mg daily, followed by imatinib [C]min assessment. Patients considered underdosed ([C]min < 1000 ng/mL) were randomized in a dose-increase strategy aiming to reach the threshold of 1000 ng/mL (TDM arm) versus standard imatinib management (control arm). Patients with [C]min levels ≥ 1000 ng/mL were treated following current European Leukemia Net recommendations (observational arm). The primary endpoint was the rate of major molecular response (MMR, BCR::ABL1IS ≤ 0.1%) at 12 months. Out of 133 evaluable patients on imatinib 400 mg daily, 86 patients had a [C]min < 1000 ng/mL and were randomized. The TDM strategy resulted in a significant increase in [C]min values with a mean imatinib daily dose of 603 mg daily. Patients included in the TDM arm had a 12-month MMR rate of 67% (95% CI, 51−81) compared to 39% (95% CI, 24−55) for the control arm (p = 0.017). This early advantage persisted over the 3-year study period, in which we considered imatinib cessation as a censoring event. Imatinib TDM was feasible and significantly improved the 12-month MMR rate. This early advantage may be beneficial for patients without easy access to second-line TKIs.
Databáze: MEDLINE
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