Variables associated with pulmonary hypertension screened by echocardiography in chronic myeloid leukemia patients on dasatinib therapy

Abstract

BackgroundPulmonary hypertension (PH) is a rare but life-threatening adverse event (AE) of dasatinib, but the associated variables are not clear. This study aimed to explore the variables associated with PH by echocardiography in patients with chronic myeloid leukemia in the chronic phase (CML-CP) receiving dasatinib therapy.MethodsEchocardiography was performed to estimate the probability of PH and pulmonary artery systolic pressure (PASP). Binary logistic analysis and Fine–Gray hazard model were used to identify the variables associated with PH by using cross-sectional and longitudinal data.ResultsAmong the 243 patients in the cross-sectional dataset, with a median dasatinib therapy duration of 27 months, 30 (12.3%) were classified as having a high probability of PH. Increasing age (OR = 1.7, p = 0.002; OR = 1.5, p = 0.003) and pericardial effusion (OR = 4.3, p = 0.004; OR = 3.2, p = 0.014) were significantly associated with a high probability of PH and PASP ≥ 40 mmHg, respectively. Among the 161 patients in the longitudinal dataset, the 3-year cumulative incidences of a high probability of PH and PASP ≥ 40 mmHg were 9.3% and 22.1%, respectively. Pericardial effusion (HR = 3.8, p = 0.005) and cardiopulmonary comorbidities (HR = 3.2, p = 0.021) were significantly associated with a high probability of PH; increasing age (HR = 1.5, p < 0.001) and dasatinib as ≥ 3rd-line therapy (p = 0.032; 2nd-line vs. 1st-line, HR = 2.0, p = 0.200; ≥ 3rd-line vs. 1st-line, HR = 3.4, p = 0.047) were significantly associated with PASP ≥ 40 mmHg.ConclusionIncreasing age, pericardial effusion, cardiopulmonary comorbidities, and dasatinib as ≥ 3rd-line TKI therapy were associated with PH in the patients with CML-CP on dasatinib therapy.

Cancer Therapy-Associated Pulmonary Hypertension and Right Ventricular Dysfunction: Etiologies and Prognostic Implications

“…A retrospective study of 451 CML patients on dasatinib who underwent transthoracic echocardiography (TTE) found that 56 (12%) of patients had an elevated right ventricular systolic pressure (RVSP) of 40 mmHg [ 55 ]. In another of study of 243 patients treated with dasatinib, 12.3% had RVSP 40 mmHg after a median follow-up of 27 months [ 58 ]. The results of this study showed an association between pericardial effusion, cardiopulmonary comorbidities, and dasatinib as 3rd line agent (vs 1st line) were associated with PH [ 58 ].…”

“…In another of study of 243 patients treated with dasatinib, 12.3% had RVSP 40 mmHg after a median follow-up of 27 months [ 58 ]. The results of this study showed an association between pericardial effusion, cardiopulmonary comorbidities, and dasatinib as 3rd line agent (vs 1st line) were associated with PH [ 58 ]. Dasatinib-induced PAH is typically a chronic process, with a median delay from drug initiation to diagnosis of 34 months [ 54 ].…”