| Autor: |
Hyacinthe Johnson-Ansah, Benjamin Maneglier, Françoise Huguet, Laurence Legros, Martine Escoffre-Barbe, Martine Gardembas, Pascale Cony-Makhoul, Valérie Coiteux, Laurent Sutton, Wajed Abarah, Camille Pouaty, Jean-Michel Pignon, Bachra Choufi, Sorin Visanica, Bénédicte Deau, Laure Morisset, Emilie Cayssials, Mathieu Molimard, Stéphane Bouchet, François-Xavier Mahon, Franck Nicolini, Philippe Aegerter, Jean-Michel Cayuela, Marc Delord, Heriberto Bruzzoni-Giovanelli, Philippe Rousselot |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
Pharmaceutics, Vol 14, Iss 8, p 1676 (2022) |
| Druh dokumentu: |
article |
| ISSN: |
1999-4923 |
| DOI: |
10.3390/pharmaceutics14081676 |
| Popis: |
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: |
Directory of Open Access Journals |
| Externí odkaz: |
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