Relationship between Dasatinib-induced Pulmonary Hypertension and Drug Dose

Abstract

Objective Dasatinib, a second-generation tyrosine kinase inhibitor, is used for chronic myelogenous leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). It reportedly causes pulmonary arterial hypertension (PAH) and the dose-dependent induction of apoptosis in pulmonary endothelial cells. However, no report has yet discussed the relationship between dasatinib-induced PAH and drug dose. We therefore investigated the incidence of dasatinib-induced PAH and the relationship between dasatinib-PAH and drug dose in consecutive patients with CML and Ph+ ALL who took dasatinib. Methods The clinical data of 128 patients with CML (94 patients) and Ph+ ALL (34 patients) were retrospectively analyzed. Patients All patients (>17 years old) who received dasatinib from January 2009 to March 2020 at Jichi Medical University (Tochigi, Japan) were included. Patients who transferred within one month of starting dasatinib administration were excluded. Results Four (4.3%) and three (8.8%) patients developed pulmonary hypertension (PH), which was considered present when the transtricuspid pressure gradient was ! 40 mmHg, in the CML and ALL groups, respectively. No significant difference was observed between the PH onset and the administration period, cumulative dose, or daily dose of dasatinib. PH occurred in seven patients (5.5%), and the period from the start of dasatinib administration to the PH onset ranged from 7 to 39 (median: 28) months. No patients died from PH in either group. Conclusion Dasatinib-induced PAH does not occur time-or dose-dependently. When administering dasatinib, cardiovascular diagnostic modalities should be routinely checked, and PAH occurrence should be promptly detected.

Dasatinib-induced Pulmonary Hypertension

“…Studies in which PH was diagnosed by right heart catheterization reported an incidence of 0.2-0.45% ( 5 , 9 ), while studies in which PH was diagnosed mainly by echocardiography reported an incidence of 2.4-5% ( 10 , 11 ). The incidence reported by Kubota et al ( 12 ) was 5.5%, which was similar as the previous reports. One important point is that PH on echocardiography needs to be interpreted with caution.…”

“…Therefore, right heart catheterization is needed to determine if the pulmonary artery itself is involved. Finally, regarding the onset timing, Kubota et al ( 12 ) reported that neither the duration of treatment nor the total dose of dasatinib was associated with the development of PH. A previous study also showed a wide range of time from the start of dasatinib to the onset of PH, with a median of 42 months (8-74 months) reported ( 8 ).…”

Dasatinib-induced pleural effusions, pericardial effusion and pulmonary arterial hypertension: a case report

“…Currently, no risk factors or predictive factors have been identified for dasatinib-related PAH ( 10 ). This was also noted in a retrospective study by Kubota et al ( 13 ), where clinical data from 128 patients with CML (94 cases) and Ph+ ALL (34 cases) were analyzed, showing no time or dose dependency for dasatinib-induced PAH. Most cases of dasatinib-induced PAH are reversible upon discontinuation of the medication.…”

Prognostic role of hybrid PET/MRI in patient with Dasatinib-Induced Pulmonary Hypertension：A Case Report

“…Dasatinib is a second-generation tyrosine kinase inhibitor (TKI) used in the treatment of chronic myelogenous leukemia (CML) and Philadelphia-positive acute lymphoblastic leukemia (Ph + ALL). Studies have reported rare cases of dasatinib-induced PH, with an incidence rate of approximately 5.5% [13]. Most case reports suggest that dasatinib-associated PH is reversible after discontinuation of the drug.…”