Analysis of the Impact of TKI Dose Adjustment Under the Guidance of Blood Concentration Monitoring on the Efficacy, Safety and Quality of Life in Patients with CML

Background

Imatinib, nilotinib and dasatinib, as tyrosine kinase inhibitors (TKIs), have been the first choice for the treatment of chronic myeloid leukemia-chronic phase (CML-CP). TKIs, usually with a fixed doses, however, these drugs in plasma exposure height heterogeneity. Treatment of drug concentration detection (TDM) is a kind of used for individualized treatment, through adjust dosage to maximize effectiveness or effective tools to reduce TKI related adverse events.

Objective

This study analyzed the effect of TDM guided TKI dose adjustment on the efficacy, side effects and quality of life of CML-CP patients. This individualized treatment mode is expected to improve the management of CML and improve the quality of life of patients.

Method

The clinical data of 370 newly diagnosed CML-CP patients who received TKIs treatment in Nanfang Hospital, Southern Medical University from January, 2016 to June, 2023 were collected. The patients were divided into TDM group and control group according to whether they received treatment concentration monitoring. The efficacy, side effects and quality of life of the two groups were compared.

Results

⑴The pharmacokinetics of TKIs vary greatly among patients. After dose adjustment based on the trough concentration of therapeutic drugs, the variability of imatinib and nilotinib decreases, and the variability of dasatinib does not change much.⑵In the imatinib cohort (n=126), there was no significant difference in the best response rate at 3 months, 6 months and 12 months between the TDM group and the control group (P>0.05). In the nilotinib cohort (n=137), there was no significant difference in the the 3-month best response rate, the 6-month best response rate, and the 12-month best response rate between the TDM group and the control group (P>0.05). In the dasatinib cohort (n=107), the 12 month MMR rate and 12 month MR4.0 rate in the TDM group were significantly higher than those in the control group (P=0.003, P=0.017, P=0.038).⑶The most common adverse events were fluid retention (30.2%) in the imatinib cohort, rash (24.1%) in the nilotinib cohort, and pleural effusion (22.4%) in the dasatinib cohort. Most of the adverse events were grade I/II. In the imatinib cohort, the incidence of III/IV adverse reactions in the TDM group was significantly lower than that in the control group (1.5% vs 13.6%, P=0.012). The incidence of full-grade thrombocytopenia, full-grade fluid retention, and grade III/IV neutropenia in the TDM group were significantly lower than those in the control group (all P <0.05). In the nilotinib cohort, the total incidence of adverse events in the TDM group was significantly lower than that in the control group (84.7% vs 96.9%, P=0.019). The incidence of adverse events in the TDM group was significantly lower than that in the control group (P=0.042, P=0.023, P=0.022). In the dasatinib cohort, the incidence of full-grade adverse reactions and grade III/IV adverse reactions in the TDM group were significantly lower than those in the control group (P=0.043, P=0.029). The incidences of full-grade neutropenia, full-grade thrombocytopenia, grade III/IV neutropenia and full-grade pleural effusion in the TDM group were lower than those in the control group (all P <0.05).⑷ In the quality of life evaluation, the scores of mental burden and daily life impact were higher. The scores of symptom burden and daily life impact in the TDM group were lower than those in the control group (P=0.008, P=0.024).

Conclusion

TDM dose adjustment is one of the clinical reference tools to achieve the target therapeutic concentration of imatinib, nilotinib and dasatinib in CML patients. It can provide individualized treatment for patients to ensure efficacy and reduce adverse reactions, thereby improving the quality of life of patients.