A Real-World Evidence-Based Study of Long-Term Tyrosine Kinase Inhibitors Dose Reduction or Discontinuation in Patients with Chronic Myeloid Leukaemia
The therapeutic approach to chronic myeloid leukaemia (CML) has changed in recent years. As a result, a high percentage of current patients in the chronic phase of the disease almost have an average life expectancy. Treatment also aims to achieve a stable deep molecular response (DMR) that might all...
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| Format: | Article |
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MDPI AG
2023-04-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/15/5/1363 |
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| author | Alicia Martín Roldán María Del Mar Sánchez Suárez Carolina Alarcón-Payer Alberto Jiménez Morales José Manuel Puerta Puerta |
| author_facet | Alicia Martín Roldán María Del Mar Sánchez Suárez Carolina Alarcón-Payer Alberto Jiménez Morales José Manuel Puerta Puerta |
| author_sort | Alicia Martín Roldán |
| collection | DOAJ |
| description | The therapeutic approach to chronic myeloid leukaemia (CML) has changed in recent years. As a result, a high percentage of current patients in the chronic phase of the disease almost have an average life expectancy. Treatment also aims to achieve a stable deep molecular response (DMR) that might allow dose reduction or even treatment discontinuation. These strategies are often used in authentic practices to reduce adverse events, yet their impact on treatment-free remission (TFR) is a controversial debate. In some studies, it has been observed that as many as half of patients can achieve TFR after the discontinuation of TKI treatment. If TFR was more widespread and globally achievable, the perspective on toxicity could be changed. We retrospectively analysed 80 CML patients treated with tyrosine kinase inhibitor (TKI) at a tertiary hospital between 2002 and 2022. From them, 71 patients were treated with low doses of TKI, and 25 were eventually discontinued, 9 of them being discontinued without a previous dose reduction. Regarding patients treated with low doses, only 11 of them had molecular recurrence (15.4%), and the average molecular recurrence free survival (MRFS) was 24.6 months. The MRFS outcome was not affected by any of the variables examined, including gender, Sokal risk scores, prior treatment with interferon or hydroxycarbamide, age at the time of CML diagnosis, the initiation of low-dose therapy and the mean duration of TKI therapy. After TKI discontinuation, all but four patients maintained MMR, with a median follow-up of 29.2 months. In our study, TFR was estimated at 38.9 months (95% CI 4.1–73.9). This study indicates that low-dose treatment and/or TKI discontinuation is a salient, safe alternative to be considered for patients who may suffer adverse events (AEs), which hinder the adherence of TKI and/or deteriorate their life quality. Together with the published literature, it shows that it appears safe to administer reduced doses to patients with CML in the chronic phase. The discontinuation of TKI therapy once a DMR has been reached is one of the goals for these patients. The patient should be assessed globally, and the most appropriate strategy for management should be considered. Future studies are needed to ensure that this approach is included in clinical practice because of the benefits for certain patients and the increased efficiency for the healthcare system. |
| first_indexed | 2024-03-11T03:24:21Z |
| format | Article |
| id | doaj.art-58932818415e4015a784dd1712ac3874 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-11T03:24:21Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-58932818415e4015a784dd1712ac38742023-11-18T02:50:31ZengMDPI AGPharmaceutics1999-49232023-04-01155136310.3390/pharmaceutics15051363A Real-World Evidence-Based Study of Long-Term Tyrosine Kinase Inhibitors Dose Reduction or Discontinuation in Patients with Chronic Myeloid LeukaemiaAlicia Martín Roldán0María Del Mar Sánchez Suárez1Carolina Alarcón-Payer2Alberto Jiménez Morales3José Manuel Puerta Puerta4Servicio de Farmacia, Hospital Universitario Virgen de las Nieves, 18014 Granada, SpainServicio de Farmacia, Hospital Universitario Virgen de las Nieves, 18014 Granada, SpainServicio de Farmacia, Hospital Universitario Virgen de las Nieves, 18014 Granada, SpainServicio de Farmacia, Hospital Universitario Virgen de las Nieves, 18014 Granada, SpainUnidad de Gestión Clínica Hematología y Hemoterapia, Hospital Universitario Virgen de las Nieves, 18014 Granada, SpainThe therapeutic approach to chronic myeloid leukaemia (CML) has changed in recent years. As a result, a high percentage of current patients in the chronic phase of the disease almost have an average life expectancy. Treatment also aims to achieve a stable deep molecular response (DMR) that might allow dose reduction or even treatment discontinuation. These strategies are often used in authentic practices to reduce adverse events, yet their impact on treatment-free remission (TFR) is a controversial debate. In some studies, it has been observed that as many as half of patients can achieve TFR after the discontinuation of TKI treatment. If TFR was more widespread and globally achievable, the perspective on toxicity could be changed. We retrospectively analysed 80 CML patients treated with tyrosine kinase inhibitor (TKI) at a tertiary hospital between 2002 and 2022. From them, 71 patients were treated with low doses of TKI, and 25 were eventually discontinued, 9 of them being discontinued without a previous dose reduction. Regarding patients treated with low doses, only 11 of them had molecular recurrence (15.4%), and the average molecular recurrence free survival (MRFS) was 24.6 months. The MRFS outcome was not affected by any of the variables examined, including gender, Sokal risk scores, prior treatment with interferon or hydroxycarbamide, age at the time of CML diagnosis, the initiation of low-dose therapy and the mean duration of TKI therapy. After TKI discontinuation, all but four patients maintained MMR, with a median follow-up of 29.2 months. In our study, TFR was estimated at 38.9 months (95% CI 4.1–73.9). This study indicates that low-dose treatment and/or TKI discontinuation is a salient, safe alternative to be considered for patients who may suffer adverse events (AEs), which hinder the adherence of TKI and/or deteriorate their life quality. Together with the published literature, it shows that it appears safe to administer reduced doses to patients with CML in the chronic phase. The discontinuation of TKI therapy once a DMR has been reached is one of the goals for these patients. The patient should be assessed globally, and the most appropriate strategy for management should be considered. Future studies are needed to ensure that this approach is included in clinical practice because of the benefits for certain patients and the increased efficiency for the healthcare system.https://www.mdpi.com/1999-4923/15/5/1363chronic myeloid leukaemiatyrosine kinase inhibitorstreatment-free remissionmolecular recurrence-free survivallow doseadverse event |
| spellingShingle | Alicia Martín Roldán María Del Mar Sánchez Suárez Carolina Alarcón-Payer Alberto Jiménez Morales José Manuel Puerta Puerta A Real-World Evidence-Based Study of Long-Term Tyrosine Kinase Inhibitors Dose Reduction or Discontinuation in Patients with Chronic Myeloid Leukaemia Pharmaceutics chronic myeloid leukaemia tyrosine kinase inhibitors treatment-free remission molecular recurrence-free survival low dose adverse event |
| title | A Real-World Evidence-Based Study of Long-Term Tyrosine Kinase Inhibitors Dose Reduction or Discontinuation in Patients with Chronic Myeloid Leukaemia |
| title_full | A Real-World Evidence-Based Study of Long-Term Tyrosine Kinase Inhibitors Dose Reduction or Discontinuation in Patients with Chronic Myeloid Leukaemia |
| title_fullStr | A Real-World Evidence-Based Study of Long-Term Tyrosine Kinase Inhibitors Dose Reduction or Discontinuation in Patients with Chronic Myeloid Leukaemia |
| title_full_unstemmed | A Real-World Evidence-Based Study of Long-Term Tyrosine Kinase Inhibitors Dose Reduction or Discontinuation in Patients with Chronic Myeloid Leukaemia |
| title_short | A Real-World Evidence-Based Study of Long-Term Tyrosine Kinase Inhibitors Dose Reduction or Discontinuation in Patients with Chronic Myeloid Leukaemia |
| title_sort | real world evidence based study of long term tyrosine kinase inhibitors dose reduction or discontinuation in patients with chronic myeloid leukaemia |
| topic | chronic myeloid leukaemia tyrosine kinase inhibitors treatment-free remission molecular recurrence-free survival low dose adverse event |
| url | https://www.mdpi.com/1999-4923/15/5/1363 |
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