Long-Term Assessment of Dasatinib-Induced Pulmonary Arterial Hypertension in Chronic Myeloid Leukemia

Abstract

▪Background: To explore a real incidence of dasatinib-induced pulmonary arterial hypertension (D-PAH) in clinical practice, we investigated 82 imatinib or other 2G tyrosine kinase inhibitor (TKI)-failed chronic myeloid leukemia (CML) patients who received dasatinib as a second-line therapy.Methods: Routine chest X-ray and Doppler echocardiography were regularly evaluated in all patients and additional tests were performed if dyspnea developed on treatment.Results: Median age at the time of starting dasatinib was 48 (16-82) years. Of 82 patients, 8 patients (9.8%) showed an elevation of right ventricular systolic pressure (RVSP>35mmHg) by Doppler echocardiography. Among them, 7 patients (8.5%) were considered D-PAH with a median dasatinib treatment duration of 32.6 (10.3-108.7) months. They underwent follow-up Doppler echocardiography median 5 (2-9) times.Five patients showed severe D-PAH (RVSP >70mmHg), 1 was moderate (RVSP 46mmHg), and 1 was mild (RVSP 41mmHg). Advanced studies such as pulmonary angiographic catheterization (patient 1 and 2) or pulmonary arterial computed tomography (patient 3 and 4) were performed for confirming D-PAH or ruling out PAH due to pulmonary vascular abnormality. Six patients had bilateral pleural effusion and 1 had unilateral pleural effusion. With sildenafil (n=5) + dose reduction (n=1) + switch to other TKI (n=6), all of patients improved dyspnea, and RVSP level was completely resolved in 3 patients. In addition, previous nilotinib therapy and concomitant pleural effusion were significant contributing factors for D-PAH.Conclusion: Regardless of complete resolution of pleural effusion, a patient with sustained dyspnea on dasatinib treatment should be carefully evaluated by Doppler echocardiography and a regular monitoring will be needed for early intervention.Abstract 5535. Table 1Characteristics of patients with dasatinib-induced PAHCohortAge at PAH diagnosis (year)SexTreatment duration before dasatinib (month)Previous therapy for CMLDuration between initiation of dasatinib and diagnosis of PAH (month)Daily mean dose of dasatinib (mg/d)Duration between diagnosis of D-PAH and last follow up (month)Treatment of D-PAHSwitch to other TKIOutcome153M54.4Interferon, Hydroxyurea, Imatinib, nilotinib26.412373.5Sildenafilnilotinib and ponatinibpartial250M36.6Interferon, Hydroxyurea, Imatinib, dasatinib, nilotinib50.311255.2Sildenafilnilotinib and radotinibpartial337F31.7Imatinib, nilotinib21.78839.7SildenafilDose de-escalationradotinibpartial445M70.9Hydroxyurea, Imatinib69.810135.2SildenafilDose de-escalationponatinibcomplete559F107.4Interferon, Hydroxyurea, Imatinib83.69214.3noneradotinibpartial646F12.6Imatinib29.17613.0Steroid, Sildenafilradotinibcomplete738F30.2Imatinib33.19810.2Dose reductionNAcomplete DisclosuresNo relevant conflicts of interest to declare.