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 1.

Characteristics of patients with dasatinib-induced PAH

CohortAge 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 TKIOutcome
1 53 M 54.4 Interferon, Hydroxyurea, Imatinib, nilotinib 26.4 123 73.5 Sildenafil nilotinib and ponatinib partial 
2 50 M 36.6 Interferon, Hydroxyurea, Imatinib, dasatinib, nilotinib 50.3 112 55.2 Sildenafil nilotinib and radotinib partial 
3 37 F 31.7 Imatinib, nilotinib 21.7 88 39.7 Sildenafil
Dose de-escalation 		radotinib partial 
4 45 M 70.9 Hydroxyurea, Imatinib 69.8 101 35.2 Sildenafil
Dose de-escalation 		ponatinib complete 
5 59 F 107.4 Interferon, Hydroxyurea, Imatinib 83.6 92 14.3 none radotinib partial 
6 46 F 12.6 Imatinib 29.1 76 13.0 Steroid, Sildenafil radotinib complete 
7 38 F 30.2 Imatinib 33.1 98 10.2 Dose reduction NA complete 
CohortAge 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 TKIOutcome
1 53 M 54.4 Interferon, Hydroxyurea, Imatinib, nilotinib 26.4 123 73.5 Sildenafil nilotinib and ponatinib partial 
2 50 M 36.6 Interferon, Hydroxyurea, Imatinib, dasatinib, nilotinib 50.3 112 55.2 Sildenafil nilotinib and radotinib partial 
3 37 F 31.7 Imatinib, nilotinib 21.7 88 39.7 Sildenafil
Dose de-escalation 		radotinib partial 
4 45 M 70.9 Hydroxyurea, Imatinib 69.8 101 35.2 Sildenafil
Dose de-escalation 		ponatinib complete 
5 59 F 107.4 Interferon, Hydroxyurea, Imatinib 83.6 92 14.3 none radotinib partial 
6 46 F 12.6 Imatinib 29.1 76 13.0 Steroid, Sildenafil radotinib complete 
7 38 F 30.2 Imatinib 33.1 98 10.2 Dose reduction NA complete 
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Disclosures

No relevant conflicts of interest to declare.

Topics:
dasatinib, leukemia, myelocytic, chronic, pulmonary arterial hypertension, imatinib mesylate, nilotinib, sildenafil, doppler echocardiography, hydroxyurea, pleural effusion, protein-tyrosine kinase inhibitor

Author notes

*

Asterisk with author names denotes non-ASH members.

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© 2014 by The American Society of Hematology
2014
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