PMID- 37242605
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230530
IS  - 1999-4923 (Print)
IS  - 1999-4923 (Electronic)
IS  - 1999-4923 (Linking)
VI  - 15
IP  - 5
DP  - 2023 Apr 28
TI  - A Real-World Evidence-Based Study of Long-Term Tyrosine Kinase Inhibitors Dose 
      Reduction or Discontinuation in Patients with Chronic Myeloid Leukaemia.
LID - 10.3390/pharmaceutics15051363 [doi]
LID - 1363
AB  - 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.
FAU - Martin Roldan, Alicia
AU  - Martin Roldan A
AUID- ORCID: 0009-0002-1185-694X
AD  - Servicio de Farmacia, Hospital Universitario Virgen de las Nieves, 18014 Granada, 
      Spain.
FAU - Sanchez Suarez, Maria Del Mar
AU  - Sanchez Suarez MDM
AUID- ORCID: 0009-0003-9517-0351
AD  - Servicio de Farmacia, Hospital Universitario Virgen de las Nieves, 18014 Granada, 
      Spain.
FAU - Alarcon-Payer, Carolina
AU  - Alarcon-Payer C
AUID- ORCID: 0000-0001-5836-1050
AD  - Servicio de Farmacia, Hospital Universitario Virgen de las Nieves, 18014 Granada, 
      Spain.
FAU - Jimenez Morales, Alberto
AU  - Jimenez Morales A
AD  - Servicio de Farmacia, Hospital Universitario Virgen de las Nieves, 18014 Granada, 
      Spain.
FAU - Puerta Puerta, Jose Manuel
AU  - Puerta Puerta JM
AD  - Unidad de Gestion Clinica Hematologia y Hemoterapia, Hospital Universitario 
      Virgen de las Nieves, 18014 Granada, Spain.
LA  - eng
PT  - Journal Article
DEP - 20230428
PL  - Switzerland
TA  - Pharmaceutics
JT  - Pharmaceutics
JID - 101534003
PMC - PMC10222180
OTO - NOTNLM
OT  - adverse event
OT  - chronic myeloid leukaemia
OT  - low dose
OT  - molecular recurrence-free survival
OT  - real-word evidence
OT  - treatment-free remission
OT  - tyrosine kinase inhibitors
COIS- The authors declare no conflict of interest.
EDAT- 2023/05/27 09:42
MHDA- 2023/05/27 09:43
PMCR- 2023/04/28
CRDT- 2023/05/27 01:29
PHST- 2023/01/14 00:00 [received]
PHST- 2023/04/25 00:00 [revised]
PHST- 2023/04/27 00:00 [accepted]
PHST- 2023/05/27 09:43 [medline]
PHST- 2023/05/27 09:42 [pubmed]
PHST- 2023/05/27 01:29 [entrez]
PHST- 2023/04/28 00:00 [pmc-release]
AID - pharmaceutics15051363 [pii]
AID - pharmaceutics-15-01363 [pii]
AID - 10.3390/pharmaceutics15051363 [doi]
PST - epublish
SO  - Pharmaceutics. 2023 Apr 28;15(5):1363. doi: 10.3390/pharmaceutics15051363.