A therapeutic drug monitoring (TDM) approach to treatment with dasatinib was shown to be associated with reduced rates of pleural effusion in patients treated for newly diagnosed chronic phase-chronic myeloid leukemia (CP-CML), although the study did not meet its primary endpoint for significant adverse events (AEs). The study reaults were published in the British Journal of Haematology.
The study was the OPTIM-dasatinib trial (ClinicalTrials.gov Identifier: NCT01916785), which examined the impact of TDM on significant AEs of treatment with dasatinib for CP-CML. The starting dose of dasatinib was 100 mg per day. After an assessment of the minimum concentration of dasatinib in the blood (Cmin), patients who were over dosed with dasatanib (Cmin ≥3 nmol/L) were assigned to either continuation of standard dose (control arm) or a dose-reduction strategy (TDM arm). Other patients remained in an observational arm.
The primary endpoint of the study was the cumulative rate of dasatinib-related significant AEs at 12 months. These included grade 3 or 4 fluid retention, any-grade pleural effusion, grade 3 or 4 hematologic toxicities, and/or any-grade AEs resulting in discontinuation.
A total of 287 patients with CML were evaluable for analysis, with 80 being randomly assigned to either the control arm or the TDM arm. Molecular response rates were statistically similar across study arms.
The study did not meet its primary endpoint, reportedly owing to hematologic toxicities that began in the first 3 months after dasatinib initiation, prior to completion of dose optimization in the TDM arm. The 12-month cumulative incidence of significant AEs in the TDM arm was 37% (95% CI, 24-54); whereas in the control arm, it was 41% (95% CI, 28-57); and in the observational arm, it was 29% (95% CI, 23-36).
The cumulative incidence of pleural effusion, however, was significantly lower for patients in the TDM arm, compared with those in the control arm at 3 time points (P =.0094). The TDM arm group showed any-grade pleural effusion at rates of 4%, 11%, and 12% at 12, 24, and 36 months, respectively. For the control group, these rates were 15%, 35%, and 39%, respectively.
The study authors concluded the trial showed TDM with dasatinib was feasible at a large scale for first-line treatment of patients with CP-CML and that TDM may have value in control of pleural effusion in these patients.
Disclosures: Some authors have declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.
Rousselot P, Mollica L, Guilhot J, et al. Dasatinib dose optimisation based on therapeutic drug monitoring reduces pleural effusion rates in chronic myeloid leukaemia patients. Br J Haematol. Published online June 30, 2021. doi:10.1111/bjh.17654